Nucleus Accumbens Core (nucleus + accumben_core)

Distribution by Scientific Domains

Selected Abstracts

Changes in hyporesponsiveness to acute amphetamine and age differences in tyrosine hydroxylase immunoreactivity in the brain over adolescence in male and female rats

Iva Z. Mathews
Abstract We investigated hyposensitivity after amphetamine in early (postnatal Day 30; P30) and late (P45) adolescent rats compared to adults (P70) in experiment 1. Locomotor activity was measured for 1,hr after the first (acute) and second (24,hr later) injection of amphetamine (0.5 or 1.5,mg/kg). P30 and P45 rats were transiently hypoactive compared to adults, as indicated by reduced locomotor activity after acute amphetamine and enhanced activity after the second injection in adolescents only. In experiment 2, ovariectomy did not alter locomotor activity during habituation at any age compared to intact rats, and, as for intact adolescents, ovariectomized adolescents continued to be less active after amphetamine than adults, suggesting gonadal immaturity alone cannot account for age differences in experiment 1. However, ovariectomy attenuated the increase in activity after the second treatment. In experiment 3 involving untreated rats, tyrosine hydroxylase immunoreactivity was reduced in P30, P40, and P50 compared to P90 rats in the nucleus accumbens core and the medial prefrontal cortex. Thus, adolescents may have an increased threshold of behavioral activation that can be overcome with either a higher dose or with repeated amphetamine treatment, and may be related to changes in the dopamine system over development. 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 417,428, 2009. [source]

Contrasting effects of selective lesions of nucleus accumbens core or shell on inhibitory control and amphetamine-induced impulsive behaviour

E. R. Murphy
Abstract The core and shell subregions of the nucleus accumbens receive differential projections from areas of the medial prefrontal cortex that have dissociable effects on impulsive and perseverative responding. The contributions of these subregions to simple instrumental behaviour, inhibitory control and behavioural flexibility were investigated using a ,forced choice' task, various parameter manipulations and an omission schedule version of the task. Post-training, selective core lesions were achieved with microinjections of quinolinic acid and shell lesions with ibotenic acid. After a series of behavioural task manipulations, rats were re-stabilized on the standard version of the task and challenged with increasing doses of d - amphetamine (vehicle, 0.5 or 1.0 mg/kg i.p. 30 min prior to test). Neither core- nor shell-lesioned rats exhibited persistent deficits in simple instrumental behaviour or challenges to behavioural flexibility or inhibitory control. Significant differences between lesion groups were unmasked by d- amphetamine challenge in the standard version of the forced task. Core lesions potentiated and shell lesions attenuated the dose-dependent effect of d- amphetamine on increasing anticipatory responses seen in sham rats. These data imply that the accumbens core and shell subregions do not play major roles in highly-trained task performance or in challenges to behavioural control, but may have opposed effects following d- amphetamine treatment. Specifically, they suggest the shell subregion to be necessary for dopaminergic activation driving amphetamine-induced impulsive behaviour and the core subregion for the normal control of this behaviour via conditioned influences. [source]

Stimulation of D1-like or D2 dopamine receptors in the shell, but not the core, of the nucleus accumbens reinstates cocaine-seeking behaviour in the rat

Heath D. Schmidt
Abstract Although increases in dopamine transmission in the brain are clearly involved in the reinstatement of cocaine seeking, the role of nucleus accumbens dopamine in cocaine priming-induced reinstatement remains controversial. The goal of these experiments was to evaluate the relative contributions of D1-like and D2-like dopamine receptors in the nucleus accumbens core and shell in the reinstatement of cocaine-seeking behaviour. Initially, rats were trained to press a lever for cocaine (0.25 mg, i.v.) using a fixed-ratio 5 (FR5) schedule of reinforcement. Responding was then extinguished by substituting saline for cocaine. During the reinstatement phase, subtype-specific dopamine receptor agonists were microinjected into the nucleus accumbens core or medial shell in order to assess their ability to induce cocaine seeking. Administration of the D1/D5 dopamine receptor agonist SKF-81297 (1.0 g) into the nucleus accumbens shell, but not core, reinstated drug-seeking behaviour. Similarly, microinjection of quinpirole (3.0 g), a D2/D3 dopamine receptor agonist, into the nucleus accumbens shell and not core reinstated drug-seeking behaviour. In contrast, administration of the D3- or D4-preferring dopamine receptor agonists PD 128,907 (1.5 and 3.0 g) and PD 168,077 (0.3 and 3.0 g), respectively, did not promote reinstatement when administered into either the core or the shell. Taken together, these results indicate that activation of D1/D5 or D2 dopamine receptors, in the limbic shell subregion of the nucleus accumbens but not the basal ganglia-orientated accumbens core, promotes the reinstatement of cocaine-seeking behaviour. [source]

Double dissociation of the effects of selective nucleus accumbens core and shell lesions on impulsive-choice behaviour and salience learning in rats

Helen H. J. Pothuizen
Abstract The nucleus accumbens can be subdivided into at least two anatomically distinct subregions: a dorsolateral ,core' and a ventromedial ,shell', and this distinction may extend to a functional dissociation. Here, we contrasted the effects of selective excitotoxic core and medial shell lesions on impulsive-choice behaviour using a delayed reward choice paradigm and a differential reward for low rates of responding (DRL) test, against a form of salience learning known as latent inhibition (LI). Core lesions led to enhanced impulsive choices as evidenced by a more pronounced shift from choosing a continuously reinforced lever to a partially reinforced lever, when a delay between lever press and reward delivery was imposed selectively on the former. The core lesions also impaired performance on a DRL task that required withholding the response for a fixed period of time in order to earn a reward. Medial shell lesions had no effect on these two tasks, but abolished the LI effect, as revealed by the failure of stimulus pre-exposure to retard subsequent conditioning to that stimulus in an active avoidance procedure in the lesioned animals. As expected, selective core lesions spared LI. The double dissociations demonstrated here support a functional segregation between nucleus accumbens core and shell, and add weight to the hypothesis that the core, but not the shell, subregion of the nucleus accumbens is preferentially involved in the control of choice behaviour under delayed reinforcement conditions and in the inhibitory control of goal-directed behaviour. [source]

Involvement of NMDA and AMPA/KA receptors in the nucleus accumbens core in instrumental learning guided by reward-predictive cues

Christian Giertler
Abstract The use of reward-predictive cues to guide behavior critically involves the nucleus accumbens. However, little is known regarding the role of ionotropic glutamate receptors in the core subregion of the nucleus accumbens (AcbC) in instrumental learning guided by reward-predictive cues. Here we examined the effects of an intra-AcbC blockade of NMDA and AMPA/KA receptors on the acquisition of an instrumental response in a reaction time (RT) task in rats. In this task, discriminative cues signaled in advance the upcoming reward magnitude (5 or 1 food pellet) associated with a lever release. During early acquisition (days 1,6) rats received daily bilateral injections of either the NMDA receptor antagonist AP5 (5.0 g per side, n = 14), the AMPA/KA receptor antagonist CNQX (2.5 g per side, n = 14) or vehicle (0.5 L per side, n = 19). No treatment was given during late acquisition (days 7,12). The main result was that rats which received intra-AcbC injections of AP5 or CNQX during early acquisition exhibited a general RT increase of responses to high and low reward. However, treatment with AP5 and CNQX did not interfere with discriminative guidance of RTs by cue-associated reward magnitudes, i.e. during acquisition RTs of responses to expected high reward became significantly faster than RTs of responses to expected low reward. Our findings suggest that NMDA and AMPA/KA receptors in the AcbC play a critical role in invigorating responding during instrumental learning, but seem less important in guiding responding according to reward-predictive cues. [source]

Modifications in DARPP-32 phosphorylation pattern after repeated palatable food consumption undergo rapid habituation in the nucleus accumbens shell of non-food-deprived rats

Barbara Danielli
Abstract In non-food-deprived rats a palatable meal induces a transient increase in dopamine output in the prefrontal cortex and nucleus accumbens shell and core; habituation to this response develops with a second palatable meal, selectively in the shell, unless animals are food-deprived. A palatable meal also induces time-dependent modifications in the dopamine and cAMP-regulated phosphoprotein of Mr 32 000 (DARPP-32) phosphorylation pattern that are prevented when SCH 23390, a selective dopamine D1 receptor antagonist, is administered shortly after the meal. This study investigated whether dopaminergic habituation in the shell had a counterpart in DARPP-32 phosphorylation changes. In non-food-deprived rats, two consecutive palatable meals were followed by similar sequences of modifications in DARPP-32 phosphorylation levels in the prefrontal cortex and nucleus accumbens core, while changes after the second meal were blunted in the shell. In food-deprived rats two consecutive meals also induced similar phosphorylation changes in the shell. Finally, SCH 23390 administered shortly after the first palatable meal in non-food-deprived rats inhibited DARPP-32 phosphorylation changes in response to the first meal, and prevented the habituation to a second meal in terms of dopaminergic response and DARPP-32 phosphorylation changes. Thus, dopamine D1 receptor stimulation plays a role in the development of habituation. [source]

Morphine withdrawal produces circadian rhythm alterations of clock genes in mesolimbic brain areas and peripheral blood mononuclear cells in rats

Su-xia Li
Abstract Previous studies have shown that clock genes are expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus, other brain regions, and peripheral tissues. Various peripheral oscillators can run independently of the SCN. However, no published studies have reported changes in the expression of clock genes in the rat central nervous system and peripheral blood mononuclear cells (PBMCs) after withdrawal from chronic morphine treatment. Rats were administered with morphine twice daily at progressively increasing doses for 7 days; spontaneous withdrawal signs were recorded 14 h after the last morphine administration. Then, brain and blood samples were collected at each of eight time points (every 3 h: ZT 9; ZT 12; ZT 15; ZT 18; ZT 21; ZT 0; ZT 3; ZT 6) to examine expression of rPER1 and rPER2 and rCLOCK. Rats presented obvious morphine withdrawal signs, such as teeth chattering, shaking, exploring, ptosis, and weight loss. In morphine-treated rats, rPER1 and rPER2 expression in the SCN, basolateral amygdala, and nucleus accumbens shell showed robust circadian rhythms that were essentially identical to those in control rats. However, robust circadian rhythm in rPER1 expression in the ventral tegmental area was completely phase-reversed in morphine-treated rats. A blunting of circadian oscillations of rPER1 expression occurred in the central amygdala, hippocampus, nucleus accumbens core, and PBMCs and rPER2 expression occurred in the central amygdala, prefrontal cortex, nucleus accumbens core, and PBMCs in morphine-treated rats compared with controls. rCLOCK expression in morphine-treated rats showed no rhythmic change, identical to control rats. These findings indicate that withdrawal from chronic morphine treatment resulted in desynchronization from the SCN rhythm, with blunting of rPER1 and rPER2 expression in reward-related neurocircuits and PBMCs. [source]

Region-Specific Induction of FosB/,FosB by Voluntary Alcohol Intake: Effects of Naltrexone

ALCOHOLISM, Issue 10 2010
Jing Li
Background:, ,FosB is the best characterized transcription factor induced by chronic stimulation. Although previous studies have demonstrated that chronic passive ethanol exposure alters ,FosB immunoreactivity (IR), the effect of chronic voluntary ethanol consumption on ,FosB remains unknown. Furthermore, although previous studies have demonstrated that the opioid antagonist naltrexone reduces alcohol consumption in clinical and preclinical settings, the effect of naltrexone on FosB/,FosB has not been explored. Here, we examined the effects of chronic voluntary ethanol intake and naltrexone on FosB/,FosB IR in striatal region and prefrontal cortex, and the effect of naltrexone on voluntary ethanol intake. Methods:, We utilized immunohistochemistry to define the changes in FosB/,FosB IR induced by chronic voluntary ethanol intake under a two-bottle intermittent access of 20% ethanol model and by systematic administration (intraperitoneal injection) of naltrexone in Sprague-Dawley rats. Results:, Chronic (15 drinking sessions in 35 days) voluntary ethanol intake robustly induces FosB/,FosB IR in nucleus accumbens core, dorsolateral striatum, and orbitofrontal cortex, but not in nucleus accumbens shell, dorsomedial striatum, and medial prefrontal cortex. Systemic administration of naltrexone for 6 days significantly reduced voluntary ethanol consumption and FosB/,FosB IR induced by chronic voluntary ethanol intake. Conclusion:, Our results suggest that chronic voluntary ethanol intake induces FosB/,FosB IR in a subregion-specific manner which involves the activation of endogenous opioid system. [source]

CB1 Receptor Blockade Decreases Ethanol Intake and Associated Neurochemical Changes in Fawn-Hooded Rats

ALCOHOLISM, Issue 1 2010
Teresa Femena
Background:, This study was undertaken to identify the neurochemical changes underlying the attenuation of voluntary ethanol intake induced by the cannabinoid CB1 receptor antagonist AM251 in fawn-hooded rats. Methods:, Rats were exposed to the 2-bottle-choice paradigm (ethanol 10% v/v or water) for 15 days. After this period, rats received AM251 (3 to 6 mg/kg, i.p.) or vehicle. Results:, Voluntary ethanol intake decreased (30%) with the administration of incremental dosages of AM251 (3 mg/kg, 5 days and 6 mg/kg, 5 days) in rats with acquired high preferring ethanol consumption (>3.5 g of ethanol/kg/d). Ethanol intake significantly decreased proopiomelanocortin expression in the arcuate nucleus (38.31%) and ,-opioid-DAMGO-stimulated [35S]-GTP, binding in the caudate-putamen (40%), nucleus accumbens core (AccC) (32.87%), and shell (AccS) (34.21%). Moreover, ethanol intake increased tyrosine hydroxylase (TH) gene expression in the substantia nigra (24%) and ventral tegmental area (23%) and corticotrophin-releasing gene expression in the paraventricular hypothalamic nucleus (41.6%). The reduction of ethanol intake induced by AM251 was associated with blockade or significant reduction of the changes produced by ethanol in the expression of these genes in key regions related to drug dependence. Interestingly, treatment with AM251 reduced (20%) TH gene expression in rats drinking only water. In this respect, the action of AM251 in reducing TH gene expression may not be specific. Conclusion:, Taken together, these results revealed that blockade of cannabinoid CB1 receptors (CB1r) decreased voluntary ethanol intake in ethanol-habituated rats by normalizing the neurochemical alterations induced by ethanol. [source]