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Conditioned Stimulus (conditioned + stimulus)
Selected AbstractsCross-Modal transfer of the conditioned eyeblink response during interstimulus interval discrimination training in young ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 7 2008Kevin L. Brown Abstract Eyeblink classical conditioning (EBC) was observed across a broad developmental period with tasks utilizing two interstimulus intervals (ISIs). In ISI discrimination, two distinct conditioned stimuli (CSs; light and tone) are reinforced with a periocular shock unconditioned stimulus (US) at two different CS,US intervals. Temporal uncertainty is identical in design with the exception that the same CS is presented at both intervals. Developmental changes in conditioning have been reported in each task beyond ages when single-ISI learning is well developed. The present study sought to replicate and extend these previous findings by testing each task at four separate ages. Consistent with previous findings, younger rats (postnatal day,PD23 and 30) trained in ISI discrimination showed evidence of enhanced cross-modal influence of the short CS,US pairing upon long CS conditioning relative to older subjects. ISI discrimination training at PD43,47 yielded outcomes similar to those in adults (PD65,71). Cross-modal transfer effects in this task therefore appear to diminish between PD30 and PD43,47. Comparisons of ISI discrimination with temporal uncertainty indicated that cross-modal transfer in ISI discrimination at the youngest ages did not represent complete generalization across CSs. ISI discrimination undergoes a more protracted developmental emergence than single-cue EBC and may be a more sensitive indicator of developmental disorders involving cerebellar dysfunction. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 647-664, 2008. [source] Associative learning and memory in a chimpanzee fetus: Learning and long-lasting memory before birthDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2004Nobuyuki Kawai Abstract We tested whether a chimpanzee fetus could form an association between an extrauterine tone and vibroacoustic stimulation (VAS) using classical conditioning treatment. Two kinds of pure tone were used as the conditioned stimuli, one where a 500-Hz tone was always followed by a VAS of 80 Hz (110 gal), the unconditioned stimulus (US), and another where a 1000-Hz tone was never followed by a VAS. This treatment was repeated 156 times in total until natural labor at 233 days of gestational age. Behavioral tests on the 33rd and 58th days after birth revealed a differential response to the tones: The infant displayed an exaggerated response to the 500-Hz tone, but not to the 1000-Hz tone. Other naïve chimpanzee infants did not show any response to either tone, which suggests that a chimpanzee fetus can distinguish between tones and form an association, and that it retains such information for at least 2 months after birth. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 116,122, 2004. [source] REM sleep: a sensitive index of fear conditioning in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005Sushil K. Jha Abstract To examine the influence of conditioned fear stimuli on sleep-wake states, we recorded sleep in Sprague,Dawley rats after exposure to tones previously paired with footshock. After habituation to a recording chamber and the recording procedure, a baseline sleep recording was obtained the next day. One day later, experimental animals were exposed to shock training designed to induce conditioned fear (FC), consisting of five tone-footshock pairings. The 5-s tones (conditioned stimuli; CS) co-terminated with 1-s footshocks (unconditioned stimuli; US). The next day sleep was recorded for 4 h in the recording chamber after presentation of five CSs alone. Sleep efficiency (total sleep time/recording period) and REM sleep (REM) and non-REM (NREM) measures were determined. While sleep efficiency was not significantly changed after CS presentation, the percentage of total sleep time spent in REM (REM percentage) was reduced in the FC animals. The reduction in REM percentage in the FC animals was due to a decrease in the number of REM bouts. In a separate experiment, we repeated the procedures, except the tones and shocks were presented in an explicitly unpaired (UP) fashion. The next day, presentation of the tones increased REM percentage in the UP group. Results are discussed in terms of the decreases in REM as a response to conditioned fear, and the relevance of these findings to the sleep changes seen in post-traumatic stress disorder (PTSD). [source] Alterations in behaviour and glutamate transmission following presentation of stimuli previously associated with cocaine exposureEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2001Gregory Hotsenpiller Abstract To study the role of glutamate in cocaine-conditioned responses, we developed a rat model in which conditioned locomotion is produced by repeated pairing of cocaine with discrete stimuli (flashing light and metronome). ,Paired' subjects received cocaine (15 mg/kg) prior to six exposures to stimuli for 30 min in the test environment. ,Unpaired' subjects received equivalent presentations of the stimuli yet received cocaine in home cages. Tests with the stimuli alone demonstrated that the conditioned locomotion displayed by Paired subjects was evident at 3 or 10 days post-training and resistant to two sessions of testing. The degree of conditioned locomotion was not correlated with the subjects' response to novelty or cocaine. Administration of the noncompetitive AMPA receptor antagonist GYKI 52466 (2.5 mg/kg, a dose without effect on spontaneous activity) attenuated the expression of conditioned activity. In vivo microdialysis revealed that Paired subjects had significantly lower basal glutamate levels in the nucleus accumbens (NAc) than did Unpaired subjects when no stimuli were presented. Presentation of the conditioned stimuli resulted in significant increases in glutamate levels in the NAc in the Paired group whilst glutamate levels in the Unpaired group remained unchanged. The associative control of glutamate levels in the NAc by stimuli formerly paired with a drug of abuse is an unprecedented finding. It is likely to reflect the convergence of excitatory inputs that the NAc receives from limbic structures. [source] Disrupting basolateral amygdala function impairs unconditioned freezing and avoidance in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2001Almira Vazdarjanova Abstract Lesions of the lateral/basolateral amygdala nuclei (BLC) disrupt freezing behaviour in response to explicit or contextual cues (conditioned stimuli , CS) paired previously with footshock (unconditioned stimulus). This deficit in expression of defensive behaviour in response to conditioned stimuli is often interpreted as inability of lesioned rats to learn CS,US associations. However, findings of several studies indicate that BLC-lesioned rats can rapidly learn CS,US associations. Such findings suggest that lesioned rats can learn CS,US associations but are impaired in the expression of freezing behaviour. In the present study we report that both temporary inactivation (lidocaine) and permanent excitotoxic (NMDA) lesions of the BLC impair the unconditioned freezing and avoidance behaviours of rats in response to a novel fear-eliciting stimulus, a ball of cat hair. These findings suggest that the BLC influences the expression of freezing and avoidance behaviours, and/or that it potentiates rats' experience of fear. Along with prior evidence of spared memory for aversive learning after BLC lesions, these findings suggest that disrupted freezing to conditioned cues in BLC-lesioned rats does not necessarily reflect inability to form CS,US associations. [source] Eyeblink conditioning using cochlear nucleus stimulation as a conditioned stimulus in developing ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 7 2008John H. Freeman Abstract Previous studies demonstrated that the development of auditory conditioned stimulus (CS) input to the cerebellum may be a neural mechanism underlying the ontogenetic emergence of eyeblink conditioning in rats. The current study investigated the role of developmental changes in the projections of the cochlear nucleus (CN) in the ontogeny of eyeblink conditioning using electrical stimulation of the CN as a CS. Rat pups were implanted with a bipolar stimulating electrode in the CN and given six 100-trial training sessions with a 300 ms stimulation train in the CN paired with a 10 ms periorbital shock unconditioned stimulus (US) on postnatal days (P) 17,18 or 24,25. Control groups were given unpaired presentations of the CS and US. Rats in both age groups that received paired training showed significant increases in eyeblink conditioned responses across training relative to the unpaired groups. The rats trained on P24,25, however, showed stronger conditioning relative to the group trained on P17,18. Rats with missed electrodes in the inferior cerebellar peduncle or in the cerebellar cortex did not show conditioning. The findings suggest that developmental changes in the CN projections to the pons, inferior colliculus, or medial auditory thalamus may be a neural mechanism underlying the ontogeny of auditory eyeblink conditioning. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 640-646, 2008. [source] Development of learned flavor preferencesDEVELOPMENTAL PSYCHOBIOLOGY, Issue 5 2006Kevin P. Myers Abstract Rats, like humans, are born with only a few innate flavor preferences and aversions. Preferences retain great plasticity throughout the lifespan because they are sensitive to modification by experience. From an early age, rats can rapidly learn to prefer or avoid a flavor (conditioned stimulus, CS) that is associated with a positive or negative unconditioned stimulus (US). The US may be the mother's milk, social or thermotactile stimulation, or other food-related stimuli. Flavor-flavor learning occurs when the CS flavor is mixed with a naturally preferred (e.g., sweet) or avoided (e.g., bitter) US flavor. Flavor preferences and aversions are also produced by USs that have postoral positive (e.g., nutritious) or negative (e.g., toxic) actions. These types of learning appear to involve different behavioral and neural mechanisms as indicated by differences in conditioned responses, effective temporal parameters, resistance to extinction, and neurochemical mechanisms. New evidence indicates that flavor-nutrient preference learning can occur before weaning and influence food selection after weaning. Flavor conditioning not only affects food choice, but can also significantly increase food acceptance, that is, total consumption. Thus, from an early age, learning processes shape the feeding behavior of animals. While primarily serving an adaptive function, learning may play a role in biasing individuals towards excessive intake and weight gain. © 2006 Wiley Periodicals, Inc. Dev Psychobiol 48: 380,388, 2006. [source] Emergence of long-term memory for conditioned aversion in the rat fetusDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2004Nadège Gruest Abstract Pregnant rats were subjected to garlic essential oil as the conditioned stimulus and 45 min later to LiCl as the unconditioned stimulus either on embryonic Days 15 and 16 (E15 and E16) or on 18 and 19 (E18 and E19). Control dams received only garlic, LiCl, or water. Progenies were tested on garlic drinking 6 weeks after the exposure to the stimuli via the mothers. In the E18 to 19 group, rats that were exposed to paired garlic,LiCl expressed a significant aversion for garlic. In the E15 to 16 group, no significant differences appeared between subgroups. These results confirm that an associative memory can be established before birth and suggests that this ability potentially emerges in a short time window of 3 days at the end of gestation. Moreover, it appears that a long-term memory can be acquired in utero and retained to be expressed postnatally when animals are autonomous. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 189,198, 2004. [source] Classical conditioning in the rat fetus: Involvement of mu and kappa opioid systems in the conditioned responseDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2002William P. Smotherman Abstract When the Embryonic Day 20 (E20) rat fetus is given a conditioning trial involving a paired presentation of an artificial nipple (the conditioned stimulus; CS) with an intraoral infusion of milk (the unconditioned stimulus; US), it shows evidence of classical conditioning when again exposed to the CS during a test trial. Specifically, the fetus shows fewer oral grasp responses (the conditioned response; CR) when continuously presented with the artificial nipple. The present study further investigated this classically conditioned reduction in oral grasping. Separate experiments (a) examined the time course of the reduction in oral grasping (Experiment 1), (b) characterized the time course of mu opioid (Experiment 2) and kappa opioid (Experiment 3) involvement in the CR, and (c) described changes in fetal behavior (Experiment 4) associated with mu and kappa opioid effects on responding to the artificial nipple. The results are discussed in terms of opioid involvement in establishing and maintaining early suckling behavior. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 104,115, 2002. DOI 10.1002/dev.10016 [source] The interaction of age and unconditioned stimulus intensity on long-trace conditioned flavor aversion in ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2002James R. Misanin Abstract To see if the neural representation of the conditioned stimulus (CS) is available to old-age rats beyond the time it is available to young adults, the intensity of the unconditioned stimulus (US) and the length of the CS,US interval were systematically varied in a trace conditioning experiment. Results indicated that increasing US intensity extends the interval over which trace conditioning is evident in old-age rats but not in young adults, suggesting that trace decay occurs more rapidly in young rats. Results were interpreted in terms of age differences in the workings of hypothesized biochemical timing mechanisms that may directly influence the ability to associate stimuli over trace intervals in conditioned taste-aversion procedures. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 131,137, 2002. DOI 10.1002/dev.10018 [source] Effects of insular cortex lesions on conditioned taste aversion and latent inhibition in the ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2007Christopher Roman Abstract The present study tested the hypothesis that lesions of the insular cortex of the rat retard the acquisition of conditioned taste aversions (CTAs) because of an impairment in the detection of the novelty of taste stimuli. Demonstrating the expected latent inhibition effect, nonlesioned control subjects acquired CTAs more rapidly when the conditioned stimulus (0.15% sodium saccharin) was novel rather than familiar (achieved by pre-exposure to the to-be-conditioned taste cue). However, rats with insular cortex lesions acquired taste aversions at the same slow rate regardless of whether the saccharin was novel or familiar. The pattern of behavioural deficits obtained cannot be interpreted as disruptions of taste detection or stimulus intensity, but is consistent with the view that insular cortex lesions disrupt taste neophobia, a dysfunction that consequently retards CTA acquisition because of a latent inhibition-like effect. [source] Nucleus accumbens neurons encode Pavlovian approach behaviors: evidence from an autoshaping paradigmEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2006Jeremy J. Day Abstract Environmental stimuli predictive of appetitive events can elicit Pavlovian approach responses that enhance an organism's ability to track and secure natural rewards, but may also contribute to the compulsive nature of drug addiction. Here, we examined the activity of individual nucleus accumbens (NAc) neurons during an autoshaping paradigm. One conditioned stimulus (CS+, a retractable lever presented for 10 s) was immediately followed by the delivery of a 45-mg sucrose pellet to a food receptacle, while another stimulus (CS,, a separate retractable lever presented for 10 s) was never followed by sucrose. Approach responses directed at the CS+ and CS, were recorded as lever presses and had no experimental consequence. Rats (n = 9) selectively approached the CS+ on more than 80% of trials and were surgically prepared for electrophysiological recording. Of 76 NAc neurons, 57 cells (75%) exhibited increases and/or decreases in firing rate (i.e. termed ,phasically active') during the CS+ presentation and corresponding approach response. Forty-seven percent of phasically active cells (27 out of 57) were characterized by time-locked but transient increases in cell firing, while 53% (30 out of 57) showed a significant reduction in firing for the duration of the CS+. In contrast, the same excitatory subpopulation exhibited smaller increases in activity relative to CS, onset, while the inhibitory subpopulation showed no change in firing during the CS, period. The magnitude and prevalence of cue-related neural responses reported here indicates that the NAc encodes biologically significant, repetitive approach responses that may model the compulsive nature of drug addiction in humans. [source] Repeated withdrawal from ethanol impairs acquisition but not expression of conditioned fearEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2003T. L. Ripley Abstract Repeated withdrawal from ethanol impairs acquisition of conditioned fear [Stephens, D.N., Brown, G., Duka, T. & Ripley, T.L. (2001) Eur. J. Neurosci., 14, 2023,2031]. This study further examined the effect of repeated withdrawal from ethanol on the expression and acquisition of fear conditioning. Following training, presentation of a cue associated with footshock (CS+) resulted in a suppression of operant responding for food reinforcement. In different groups, shock thresholds were manipulated to give weak or severe behavioural suppression. Rats were subsequently chronically treated with ethanol-containing liquid diet either continuously (single withdrawal) or with three withdrawal periods (repeated withdrawal). Ethanol treatment and withdrawal had no effect on conditioned suppression of responding tested 2 weeks after the final withdrawal, at either shock intensity. Nevertheless, extinction of conditioned fear was impaired in the repeated withdrawal group exposed to the higher shock intensity. In the high intensity group, the stimulus,shock association was then reversed, so that the previously neutral conditioned stimulus (CS,) became the CS+. Acquisition of suppression to the new CS+ was significantly less in the animals previously given repeated experience of withdrawal, confirming our previous finding. Thus, repeated withdrawal from ethanol lead to disruption in the acquisition of fear conditioning but had no effect on retrieval of an association formed prior to the ethanol-withdrawal experiences. [source] Trace eyeblink conditioning in decerebrate guinea pigsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2003Sadaharu Kotani Abstract We investigated the trace eyeblink conditioning in decerebrate guinea pigs to elucidate the possible role of the cerebellum and brainstem in this hippocampus-dependent task. A 350-ms tone conditioned stimulus was paired with a 100-ms periorbital shock unconditioned stimulus with a trace interval of either 0, 100, 250 or 500 ms. Decerebrate animals readily acquired the conditioned response with a trace interval of 0 or 100 ms. Even in the paradigm with a 500-ms trace interval, which is known to depend critically on the hippocampus in all animal species examined, the decerebrate guinea pigs acquired the conditioned response, which had adaptive timing as well as in the other paradigms with a shorter trace interval. However, it took many more trials to learn in the 500-ms trace paradigm than in the shorter trace interval paradigms, and the conditioned response expression was unstable from trial to trial. When decerebrate animals were conditioned step by step with a trace interval of 100, 250 and 500 ms, sequentially, they easily acquired the adaptive conditioned response to a 500-ms trace interval. However, the frequency of conditioned responses decreased after the trace interval was shifted from 250 ms to 500 ms, which was not observed after the shift from 100 ms to 250 ms. These results suggest that the cerebellum and brainstem could maintain the ,trace' of the conditioned stimulus and associate it with the unconditioned stimulus even in the 500-ms trace paradigm, but that the forebrain might be required for facilitating and stabilizing the association. [source] Impairment of eyeblink conditioning in GluR,2-mutant mice depends on the temporal overlap between conditioned and unconditioned stimuliEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2001Yasushi Kishimoto Abstract Mice lacking the glutamate receptor subunit ,2 (GluR,2) are deficient in cerebellar long-term depression (LTD) at the parallel fibre,Purkinje cell synapses. We conducted delay and trace eyeblink conditioning with these mice, using various temporal intervals between the conditioned stimulus (CS) and unconditioned stimulus (US). During trace conditioning in which a stimulus-free trace interval (TI) of 250, 100 or 50 ms intervened between the 352-ms tone CS and 100-ms US, GluR,2-mutant mice learned as successfully as wild-type mice. Even in the paradigm with TI = 0 ms, in which the end of CS and onset of US are simultaneous, there was no difference between the GluR,2-mutant and wild-type mice in their acquisition of a conditioned response. However, in the delay paradigm in which the 452-ms CS overlapped temporally with the coterminating 100-ms US, GluR,2-mutant mice exhibited severe learning impairment. The present study together with our previous work [Kishimoto, Y., Kawahara, S., Suzuki, M., Mori, H., Mishina, M. & Kirino, Y. (2001) Eur. J. Neurosci.,13, 1249,1254], indicates that cerebellar LTD-independent learning is possible in paradigms without temporal overlap between the CS and US. On the other hand, GluR,2 and cerebellar LTD are essential for learning when there is CS,US temporal overlap, suggesting that the cerebellar neural substrates underlying eyeblink conditioning may change, depending on the temporal overlap of the CS and US. [source] Deficient long-term synaptic depression in the rostral cerebellum correlated with impaired motor learning in phospholipase C ,4 mutant miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2001Mariko Miyata Abstract Long-term depression (LTD) at parallel fibre,Purkinje cell synapse of the cerebellum is thought to be a cellular substrate for motor learning. LTD requires activation of metabotropic glutamate receptor subtype 1 (mGluR1) and its downstream signalling pathways, which invariably involves phospholipase C,s (PLC,s). PLC,s consist of four isoforms (PLC,1,4) among which PLC,4 is the major isoform in most Purkinje cells in the rostral cerebellum (lobule 1 to the rostral half of lobule 6). We studied mutant mice deficient in PLC,4, and found that LTD was deficient in the rostral but not in the caudal cerebellum of the mutant. Basic properties of parallel fibre,Purkinje cell synapses and voltage-gated Ca2+ channel currents appeared normal. The mGluR1-mediated Ca2+ release induced by repetitive parallel fibre stimulation was absent in the rostral cerebellum of the mutant, suggesting that their LTD lesion was due to the defect in the mGluR1-mediated signalling in Purkinje cells. Importantly, the eyeblink conditioning, a simple form of discrete motor learning, was severely impaired in PLC,4 mutant mice. Wild-type mice developed the conditioned eyeblink response, when pairs of the conditioned stimulus (tone) and the unconditioned stimulus (periorbital shock) were repeatedly applied. In contrast, PLC,4 mutant mice could not learn the association between the conditioned and unconditioned stimuli, although their behavioural responses to the tone or to the periorbital shock appeared normal. These results strongly suggest that PLC,4 is essential for LTD in the rostral cerebellum, which may be required for the acuisition of the conditioned eyeblink response. [source] Genetic variation in brain-derived neurotrophic factor and human fear conditioningGENES, BRAIN AND BEHAVIOR, Issue 1 2009G. Hajcak Brain-derived neurotrophic factor (BDNF) has been implicated in hippocampal-dependent learning processes, and carriers of the Met allele of the Val66Met BDNF genotype are characterized by reduced hippocampal structure and function. Recent nonhuman animal work suggests that BDNF is also crucial for amygdala-dependent associative learning. The present study sought to examine fear conditioning as a function of the BDNF polymorphism. Fifty-seven participants were genotyped for the BDNF polymorphism and took part in a differential-conditioning paradigm. Participants were shocked following a particular conditioned stimulus (CS+) and were also presented with stimuli that ranged in perceptual similarity to the CS+ (20, 40 or 60% smaller or larger than the CS+). The eye blink component of the startle response was measured to quantify fear conditioning; post-task shock likelihood ratings for each stimulus were also obtained. All participants reported that shock likelihood varied with perceptual similarity to the CS+ and showed potentiated startle in response to CS ± 20% stimuli. However, only the Val/Val group had potentiated startle responses to the CS+. Met allele carrying individuals were characterized by deficient fear conditioning , evidenced by an attenuated startle response to CS+ stimuli. Variation in the BDNF genotype appears related to abnormal fear conditioning, consistent with nonhuman animal work on the importance of BDNF in amygdala-dependent associative learning. The relation between genetic variation in BDNF and amygdala-dependent associative learning deficits is discussed in terms of potential mechanisms of risk for psychopathology. [source] Perception of sweet taste is important for voluntary alcohol consumption in miceGENES, BRAIN AND BEHAVIOR, Issue 1 2008Y. A. Blednov To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: ,-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild-type mice, whereas Tas1r3 null mice were not different from wild type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion (CTA) to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in CTA to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol. [source] Time-dependent involvement of the dorsal hippocampus in trace fear conditioning in miceHIPPOCAMPUS, Issue 4 2005Ilga Misane Abstract Hippocampal and amygdaloid neuroplasticity are important substrates for Pavlovian fear conditioning. The hippocampus has been implicated in trace fear conditioning. However, a systematic investigation of the significance of the trace interval has not yet been performed. Therefore, this study analyzed the time-dependent involvement of N-methyl- D -aspartate (NMDA) receptors in the dorsal hippocampus in one-trial auditory trace fear conditioning in C57BL/6J mice. The NMDA receptor antagonist APV was injected bilaterally into the dorsal hippocampus 15 min before training. Mice were exposed to tone (conditioned stimulus [CS]) and footshock (unconditioned stimulus [US]) in the conditioning context without delay (0 s) or with CS-US (trace) intervals of 1,45 s. Conditioned auditory fear was determined 24 h after training by the assessment of freezing and computerized evaluation of inactivity in a new context; 2 h later, context-dependent memory was tested in the conditioning context. NMDA receptor blockade by APV markedly impaired conditioned auditory fear at trace intervals of 15 s and 30 s, but not at shorter trace intervals. A 45-s trace interval prevented the formation of conditioned tone-dependent fear. Context-dependent memory was always impaired by APV treatment independent of the trace interval. The results indicate that the dorsal hippocampus and its NMDA receptors play an important role in auditory trace fear conditioning at trace intervals of 15,30-s length. In contrast, NMDA receptors in the dorsal hippocampus are unequivocally involved in contextual fear conditioning independent of the trace interval. The results point at a time-dependent role of the dorsal hippocampus in encoding of noncontingent explicit stimuli. Preprocessing of long CS-US contingencies in the hippocampus appears to be important for the final information processing and execution of fear memories through amygdala circuits. © 2005 Wiley-Liss, Inc. [source] Conditioning of stress in Nile tilapiaJOURNAL OF FISH BIOLOGY, Issue 4 2004P. S. A. Moreira A Pavlovian conditioning paradigm was used to induce a connection between a conditioned stimulus, light (CS), associated with an unconditioned stimulus, confinement (US) in Nile tilapia Oreochromis niloticus, which resulted in a conditioned endocrine response (CR) to the CS alone manifested as an increase in plasma cortisol. Individual isolated Nile tilapia were submitted for 10 days to the conditioning treatment consisting of turning on a light (CS) for 1 min with subsequent 30 min confinement (US). On the 10th day of the experiment, plasma cortisol was not increased when fish were subjected to no handling at all, or only light, or even a daily stressor for the 9 days. On the other hand, at the 10th day cortisol was significantly increased only when light was presented either with or without pairing with the stressor. These results confirmed that the cue, light (CS), was not stressful in itself, but when given as the CS in the absence of the US post conditioning the hypothalamus,pituitary,interrenal axis was activated. Therefore, it was concluded that memory of a previous experience with a stressor can be recalled by a conditioned stimulus and induce stress, which is the first demonstration of a memory-induced stress in fishes. [source] Effects of d -Cycloserine on Extinction and Reconditioning of Ethanol-Seeking Behavior in MiceALCOHOLISM, Issue 5 2009Peter A. Groblewski Background:,d -Cycloserine (DCS), a partial N -methyl- d -aspartate receptor agonist, has been shown to enhance the extinction of both cocaine and amphetamine-induced conditioned place preference (CPP). However, there have been no reports of the effects of DCS on the extinction of ethanol-conditioned behaviors in mice. Thus, the current experiments examined the effects of DCS on the extinction and subsequent reconditioning of ethanol-induced CPP in mice. Methods:, Male DBA/2J mice received either 2 or 4 pairings of ethanol (2 g/kg) with a conditioned stimulus (CS+) floor cue (and an equal number of saline pairings with a CS, floor cue on alternate days) resulting in either a weak or strong ethanol CPP, respectively. Following conditioning of a strong ethanol CPP mice received saline or 30 mg/kg DCS prior to each of the twelve 30-minute choice extinction trials administered at 48-hour intervals. Mice that had received conditioning of a weak ethanol CPP received saline, 30 or 60 mg/kg DCS immediately before each of the six 30-minute choice extinction trials. Following successful ethanol CPP extinction, mice received reconditioning trials similar to the initial conditioning trials. A final experiment examined the effects 12 DCS pre-exposures (15, 30, and 60 mg/kg) on initial conditioning of ethanol CPP. Results:, First, we showed that 2 doses of DCS (30 and 60 mg/kg) did not have aversive properties that could confound the effects on extinction of CPP (Experiment 1). Second, we showed that DCS (30 and 60 mg/kg) had no effect on the rate of extinction of either strong (Experiment 2) or weak (Experiment 3) ethanol-induced CPP. Interestingly, DCS administered during extinction interfered with reconditioning of ethanol-induced CPP,an effect specific to reconditioning, as DCS pre-exposure did not influence initial ethanol CPP conditioning (Experiment 4). Conclusions:, These experiments show that although DCS showed no effect on extinction behavior, when given during extinction it interfered with subsequent reconditioning of ethanol CPP. The mechanisms of this effect were not, however, due to nonspecific interference with learning because repeated DCS pre-exposures did not impair initial conditioning of ethanol CPP. [source] Early Responsiveness to Stimuli Paired With Different Stages Within the State of Alcohol IntoxicationALCOHOLISM, Issue 5 2002Ricardo M. Pautassi Background: Infant rats quickly learn to avoid a sensory cue paired with alcohol as an unconditioned stimulus, particularly when the drug reaches peak blood concentrations. In this study, a tactile cue paired with the onset of alcohol intoxication preceded subsequent presentations of a gustatory conditioned stimulus (CS). The goal was to address the possibility of differential conditioning depending on when stimuli were introduced during the course of the toxic state. Methods: In experiment 1, rat pups received sequential presentations of a salient texture (sandpaper) and a gustatory cue (saccharin) while intoxicated with a 2.5 g/kg alcohol dose or after receiving saline. Texture location tests and saccharin intake assessments were then performed. A third modality of assessment was defined by a saccharin intake test while pups simultaneously experienced sandpaper. In experiment 2, alcohol-mediated conditioning was followed by tests similar to those of experiment 1, but after pups were re-exposed to either the tactile CS or the alcohol-unconditioned stimulus. Results: Conditioned taste aversions, due to pairing saccharin and the later stage of alcohol intoxication, were reliably established in both experiments. Also in both experiments, this excitatory aversive response was dramatically inhibited when the association between the texture CS and the earlier stage of alcohol intoxication was activated. There were no indications of conditioned motor responses to the tactile CS that might compete with intake behavior of saccharin or distort measurement of an appetitive memory derived from pairing the texture and the earlier stage of intoxication. Conclusions: Rat pups' expression of an association between a taste signaling aversive consequences of alcohol was eliminated by the presence of a tactile stimulus that originally had signaled the absence of aversive consequences of alcohol intoxication. The results suggest the interaction of inhibitory and excitatory conditioning involving the aversive properties of alcohol. [source] Ethanol as a Reinforcer in the Newborn's First Suckling ExperienceALCOHOLISM, Issue 3 2001Sarah J. Cheslock Background: Recent evidence suggests that human infants prefer alcohol-flavored milk when fed through a bottle. Animal models also indicate a surprising predisposition for neonatal and infant rats to voluntarily and willingly ingest ethanol. These findings suggest high susceptibility to the reinforcing properties of ethanol early in ontogeny. Methods: A surrogate nipple technique,a highly effective tool for investigation of the reinforcing properties of different fluids,was applied in the present study. Tests of ethanol reinforcement were accomplished in terms of two basic paradigms of Pavlovian conditioning. In one paradigm, the conditioned stimulus (CS) was the surrogate nipple, and in the other, the CS was a novel odor. Results: Newborn rats showed sustained attachment to the nipple providing 5% ethanol, and later reproduced this behavioral pattern toward the empty nipple (CS alone). Ingestion of ethanol yielding appetitive reinforcement was accompanied by detectable blood alcohol concentrations, with most in the range of 20,30 mg/dl. The reinforcing efficacy of ethanol was also confirmed in the classical olfactory conditioning paradigm: following pairing with intraoral ethanol infusions, the odor (CS) alone elicited sustained attachment to an empty nipple. Females showed better olfactory conditioning with low concentrations of ethanol, whereas males were effectively more conditioned to high concentrations. Although there were no reinforcing consequences of intraperitoneally injected ethanol [as an unconditioned stimulus (US)] when a neutral odor was the CS, when paired with ingestion of water from a nipple, the injection of ethanol had a reinforcing effect. Conclusions: The present series of experiments revealed ethanol reinforcement in the newborn rat. Two varieties of Pavlovian conditioning established that ethanol can serve as an effective US, and hence reinforcer, in such a way as to increase the approach and responsiveness toward stimuli paired with that US, indicating appetitive reinforcement. 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