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Behavioral Sensitization (behavioral + sensitization)
Selected AbstractsProopiomelanocortin Peptides Are Not Essential for Development of Ethanol-Induced Behavioral SensitizationALCOHOLISM, Issue 7 2009Amanda L. Sharpe Background:, Behavioral sensitization is a result of neuroadaptation to repeated drug administration and is hypothesized to reflect an increased susceptibility to drug abuse. Proopiomelanocortin (POMC) derived peptides including ,-endorphin and ,-melanocyte stimulating hormone have been implicated in development of behavioral sensitization and the reinforcing effects of alcohol and other drugs of abuse. This study used a genetically engineered mouse strain that is deficient for neural POMC to directly determine if any POMC peptides are necessary for the development of ethanol-induced locomotor sensitization. Methods:, Adult female mice deficient for POMC in neurons only (Pomc,/,Tg/Tg, KO) and wildtype (Pomc+/+Tg/Tg, WT) littermates were injected once daily with either saline or ethanol (i.p.) for 12 to 13 days. On ethanol test day (day 13 or 14) all mice from both treatment groups received an i.p. injection of ethanol immediately before a 15-minute analysis of locomotor activity. Blood ethanol concentration (BEC) was measured on ethanol test day immediately following the test session. Baseline locomotor activity was measured for 15 minutes after a saline injection 2 days later in both groups. Results:, There was no significant difference in BEC between genotypes (WT = 2.11 ± 0.06; KO = 2.03 ± 0.08 mg/ml). Both WT and nPOMC-deficient mice treated repeatedly with ethanol demonstrated a significant increase in locomotor activity on test day when compared to repeated saline-treated counterparts. In addition, mice of both genotypes in the repeated saline groups showed a significant locomotor stimulant response to acute ethanol injection. Conclusions:, Central POMC peptides are not required for either the acute locomotor stimulatory effect of ethanol or the development of ethanol-induced locomotor sensitization. While these peptides may modulate other ethanol-associated behaviors, they are not essential for development of behavioral sensitization. [source] PRECLINICAL STUDY: Amphetamine- and nicotine-induced cross-sensitization in adolescent rats persists until adulthoodADDICTION BIOLOGY, Issue 3 2009Gabriela C. Santos ABSTRACT Nicotine and psychostimulants are often abused in combination and drug abuse often begins during adolescence and can have long-term consequences. Behavioral sensitization has been suggested as an animal model of neuroplasticity implicated in the development of drug addiction. We evaluated whether the pretreatment with nicotine (0.4 mg/kg; s.c.) or amphetamine (5.0 mg/kg; i.p.) in adolescent rats [from postnatal day (P) 28 to P34] could induce cross-sensitization to nicotine and amphetamine when animals were challenged during both adolescence (P37) and adulthood (P70), in separate groups of animals. Adolescent animals pretreated with amphetamine displayed behavioral sensitization to nicotine, which persisted until adulthood. Moreover, adolescent animals pretreated with nicotine showed sensitized locomotor response to amphetamine in the adulthood. These data suggest that adolescents who abuse nicotine may be particularly susceptible to the effects of amphetamine and vice versa. Moreover, this increased vulnerability may persist through their development until adulthood. [source] Neural plasticity and addiction: integrin-linked kinase and cocaine behavioral sensitizationJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Qiang Chen Abstract Behavioral sensitization of psychostimulants was accompanied by alterations in a variety of biochemical molecules in different brain regions. However, which change is actually related to drug-produced sensitization lacks of accurate clarification. In this study, we investigated the role of integrin-linked kinase (ILK) in both the induction and expression of cocaine sensitization. Conditional inhibition of ILK expression was established in the nucleus accumbens (NAc) core by microinjecting recombinant adeno-associated virus-carrying, tetracycline-on-regulated small interfering RNA which reversed the chronic cocaine-induced psychomotor sensitization, as well as the changes in protein kinase B Ser473 phosphorylation, dendritic density, and dendritic spine numbers locally. Importantly, the reversed psychomotor sensitization did not recover after cessation of the silencing for 8 days. We also demonstrated that inhibition of ILK expression pre- and during-chronic cocaine treatments blocked the induction of cocaine psychomotor sensitization and abolished the stimulant effect of cocaine on ILK expression. In contrast, inhibition of ILK expression in the NAc core has no significant effect on cocaine-induced stereotypical behaviors. This concludes that ILK is involved in cocaine sensitization with the earlier induction and later expression functioning as a kinase to regulate protein kinase B Ser473 phosphorylation and a scaffolding protein to regulate the reorganization of the NAc spine morphology. [source] Proopiomelanocortin Peptides Are Not Essential for Development of Ethanol-Induced Behavioral SensitizationALCOHOLISM, Issue 7 2009Amanda L. Sharpe Background:, Behavioral sensitization is a result of neuroadaptation to repeated drug administration and is hypothesized to reflect an increased susceptibility to drug abuse. Proopiomelanocortin (POMC) derived peptides including ,-endorphin and ,-melanocyte stimulating hormone have been implicated in development of behavioral sensitization and the reinforcing effects of alcohol and other drugs of abuse. This study used a genetically engineered mouse strain that is deficient for neural POMC to directly determine if any POMC peptides are necessary for the development of ethanol-induced locomotor sensitization. Methods:, Adult female mice deficient for POMC in neurons only (Pomc,/,Tg/Tg, KO) and wildtype (Pomc+/+Tg/Tg, WT) littermates were injected once daily with either saline or ethanol (i.p.) for 12 to 13 days. On ethanol test day (day 13 or 14) all mice from both treatment groups received an i.p. injection of ethanol immediately before a 15-minute analysis of locomotor activity. Blood ethanol concentration (BEC) was measured on ethanol test day immediately following the test session. Baseline locomotor activity was measured for 15 minutes after a saline injection 2 days later in both groups. Results:, There was no significant difference in BEC between genotypes (WT = 2.11 ± 0.06; KO = 2.03 ± 0.08 mg/ml). Both WT and nPOMC-deficient mice treated repeatedly with ethanol demonstrated a significant increase in locomotor activity on test day when compared to repeated saline-treated counterparts. In addition, mice of both genotypes in the repeated saline groups showed a significant locomotor stimulant response to acute ethanol injection. Conclusions:, Central POMC peptides are not required for either the acute locomotor stimulatory effect of ethanol or the development of ethanol-induced locomotor sensitization. While these peptides may modulate other ethanol-associated behaviors, they are not essential for development of behavioral sensitization. [source] PRECLINICAL STUDY: FULL ARTICLE: Repeated ethanol administration modifies the temporal structure of sucrose intake patterns in mice: effects associated with behavioral sensitizationADDICTION BIOLOGY, Issue 3 2010Raśl Pastor ABSTRACT Neuroadaptations supporting behavioral sensitization to abused drugs are suggested to underlie pathological, excessive motivation toward drugs and drug-associated stimuli. Drug-induced sensitization has also been linked to increased appetitive responses for non-drug, natural reinforcers. The present research investigated whether ethanol (EtOH)-induced neural changes, inferred from psychomotor sensitization, can modify consumption and intake dynamics for the natural reinforcer, sucrose. The effects of EtOH-induced sensitization in mice on the temporal structure of sucrose intake patterns were measured using a lickometer system. After sensitization, sucrose intake dynamics were measured for 1 hour daily for 7 days and indicated more rapid initial approach and consumption of sucrose in EtOH-sensitized groups; animals showed a shorter latency to the first intake bout and an increased number of sucrose bottle licks during the initial 15 minutes of the 1-hour sessions. This effect was associated with increased frequency and size of bouts. For the total 1-hour session, sucrose intake and bout dynamics were not different between groups, indicating a change in patterns of sucrose intake but not total consumption. When sensitization was prevented by the ,-aminobutyric acid B receptor agonist, baclofen, the increased rate of approach and consumption of sucrose were also prevented. Thus, EtOH-induced sensitization, and not the mere exposure to EtOH, was associated with changes in sucrose intake patterns. These data are consistent with current literature suggesting an enhancing effect of drug-induced sensitization on motivational processes involved in reinforcement. [source] PRECLINICAL STUDY: BRIEF REPORT: Epigenetic modulation at the CCR2 gene correlates with the maintenance of behavioral sensitization to methamphetamineADDICTION BIOLOGY, Issue 3 2010Daigo Ikegami ABSTRACT The intermittent administration of methamphetamine produces behavioral sensitization to methamphetamine. In the limbic forebrain, mainly including the nucleus accumbens, of mice that had been intermittently treated with methamphetamine, we found a significant increase in mRNA of a chemokine, CCR2. This increase was accompanied by a significant increase in histone H3 lysine 4 (H3K4) trimethylation at its promoter. Interestingly, the maintenance of sensitization to methamphetamine-induced hyperlocomotion was significantly decreased in CCR2 knockout mice. These findings suggest that increased CCR2 associated with epigenetic modification after the intermittent administration of methamphetamine may be associated with the maintenance of sensitization to methamphetamine-induced hyperlocomotion. [source] PRECLINICAL STUDY: Amphetamine- and nicotine-induced cross-sensitization in adolescent rats persists until adulthoodADDICTION BIOLOGY, Issue 3 2009Gabriela C. Santos ABSTRACT Nicotine and psychostimulants are often abused in combination and drug abuse often begins during adolescence and can have long-term consequences. Behavioral sensitization has been suggested as an animal model of neuroplasticity implicated in the development of drug addiction. We evaluated whether the pretreatment with nicotine (0.4 mg/kg; s.c.) or amphetamine (5.0 mg/kg; i.p.) in adolescent rats [from postnatal day (P) 28 to P34] could induce cross-sensitization to nicotine and amphetamine when animals were challenged during both adolescence (P37) and adulthood (P70), in separate groups of animals. Adolescent animals pretreated with amphetamine displayed behavioral sensitization to nicotine, which persisted until adulthood. Moreover, adolescent animals pretreated with nicotine showed sensitized locomotor response to amphetamine in the adulthood. These data suggest that adolescents who abuse nicotine may be particularly susceptible to the effects of amphetamine and vice versa. Moreover, this increased vulnerability may persist through their development until adulthood. [source] Peptide signaling paths related to intoxication, memory and addictionADDICTION BIOLOGY, Issue 3 2000William E. M. Lands Many peptides bind to G protein-coupled receptors and activate intracellular signaling paths for adaptive cellular responses. The components of these paths can be affected by signals from other neurotransmitters to produce overall integrated results not easily predicted from customary a priori considerations. This intracellular cross-talk among signaling paths provides a "filter" through which long-term tonic signals affect short-term phasic signals as they progress toward the nucleus and induce long-term adaptation of gene expression which provide enduring attributes of acquired memories and addictions. Peptides of the PACAP family provide intracellular signaling that involves kinases, scaffolding interactions, Ca2 + mobilization, and gene expression to facilitate development of tolerance to alcohol and development of associative memories. The peptide-induced enhancement of NMDA receptor responses to extracellular glutamate also may increase behavioral sensitization to the low doses of alcohol that occur at the onset of each bout of drinking. Because many gene products participate in each signaling path, each behavioral response to alcohol is a polygenic process of many steps with no single gene product sufficient to interpret fully the adaptive response to alcohol. Different susceptibility of individuals to alcohol addiction may be a cumulative result of small differences among the many signaling components. Understanding this network of signals may help interpret future "magic bullets" proposed to treat addiction. [source] Role of peroxynitrite in methamphetamine-induced dopaminergic neurotoxicity and sensitization in miceADDICTION BIOLOGY, Issue 3 2000Syed F. Ali Methamphetamine (METH)-induced dopaminergic neurotoxicity is thought to be associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recently, we have reported that copper/zinc(CuZn)-superoxide dismutase transgenic mice are resistant to METH-induced neurotoxicity. In the present study, we examined the role of the neuronal nitric oxide synthase (nNOS), susceptibility of nNOS knockout (KO) mice and sensitization to psychostimulants after neurotoxic doses of METH. Male SwissWebster mice were treated with or without 7-nitroindazole (7-NI) along with METH (5 mg/kg,ip,q 3h × 3) and were sacrificed 72 h after the last METH injection. Dopamine (DA) and dopamine transporter (DAT) binding sites were determined in striatum from saline and METH-treated animals. 7-NI completely protected against the depletion of DA, and DAT in striatum. In follow-up experiments nNOS KO mice along with appropriate control (C57BL/6N, SV129 and B6JSV129) mice were treated with METH (5 mg/kg,ip, q 3h × 3) and were sacrificed 72 h after dosing. This schedule of METH administrations resulted in only 10,20% decrease in tissue content of DA and no apparent change in the number of DAT binding sites in nNOS KO mice. However, this regime of METH resulted in a significant decrease in the content of DA as well as DAT binding sites in the wild-type animals. Pre-exposure to single or multiple doses of METH resulted in a marked locomotion sensitization in response to METH. However, the nNOS KO mice show no sensitization in response to METH after single or multiple injections of METH. Therefore, these studies strongly suggest the role of peroxynitrite, nNOS and DA system in METH-induced neurotoxicity and behavioral sensitization. [source] Marker-assisted dissection of genetic influences on motor and neuroendocrine sensitization to cocaine in ratsGENES, BRAIN AND BEHAVIOR, Issue 3 2009L. F. Vendruscolo This study investigated genetic influences on behavioral and neuroendocrine responses to cocaine sensitization. We used male and female rats of the inbred strains Lewis (LEW) and spontaneously hypertensive rats (SHR), which display genetic differences in stress-related responses. The influence of two quantitative trait loci (QTL; Ofil1 and Ofil2 on chromosomes 4 and 7), which modulate stress reactivity in rats, on the effects of cocaine was also investigated through the use of recombinant lines (derived from a LEW × SHR intercross) selected by their genotype at Ofil1 and Ofil2. Animals were given repeated cocaine or saline injections and tested for locomotion (induction of sensitization). Two weeks later, all animals were challenged with cocaine, and locomotion and corticosterone levels were measured (expression of sensitization). Results indicated that male SHR rats showed more behavioral sensitization than LEW rats, whereas no strain differences in sensitization were seen among females. When challenged with cocaine, LEW and SHR rats of both sexes pretreated with cocaine showed behavioral sensitization compared with saline pretreated animals; however, only LEW rats displayed an increase in the corticosterone levels. Ofil1 was found to influence the induction of sensitization in males and Ofil2 modulated the locomotor effect of cocaine in females. This study provides evidence of a genotype-dependent relationship between the induction and expression of cocaine sensitization, and between the behavioral and neuroendocrine responses induced by cocaine. Moreover, the Ofil1 and Ofil2 loci may contain one or more genes that control the behavioral effects of cocaine in rats. [source] Hippocampus modulates the behaviorally-sensitizing effects of nicotine in a rat model of novelty-seeking: Potential role for mossy fibersHIPPOCAMPUS, Issue 10 2007Amrinder S. Bhatti Abstract Present experiments investigate interactions between a rat model of the novelty-seeking phenotype and psychomotor sensitization to nicotine (NIC) in adolescence, and the potential role of hippocampal mossy fibers in mediating the behaviorally-sensitizing effects of NIC. Outbred rats were phenotype-screened as high-responders (HR; locomotor reactivity to novelty score ranking in the upper third of the population) or low-responders (LR; locomotor reactivity to novelty score ranking in the lower third of the population). In Experiment 1, both phenotypes were trained with four NIC injections (at 3-d intervals on postnatal days 33,44), and lidocaine microinfusion was used to temporarily inactivate the hippocampal hilus at each NIC injection. Systemic saline and microinjection of artificial cerebral spinal fluid (CSF) were used as controls. During NIC training, lidocaine inactivation caused augmented locomotor response to NIC in HRs compared to LRs irrespective of injection days. Following 1 week of abstinence, all animals were challenged with a low dose of NIC. During challenge, previously NIC/CSF trained LRs and HRs were divided into two; one half receiving lidocaine inactivation of the hippocampal hilus and the other half receiving CSF control microinjection. Only HRs showed behavioral sensitization to the challenge dose of NIC, which was enhanced with lidocaine inactivation. In Experiment 2, a single NIC exposure was found sufficient to induce sensitization to the challenge dose of NIC in HRs, and concurrently an enlarged supra-pyramidal mossy fiber (SP-MF) terminal field. The increase in the SP-MF volume in HRs was greater with repeated NIC training. In both single and repeated NIC training cases, a significant positive morphobehavioral correlation was observed between challenge NIC-induced locomotion and the SP-MF terminal field volume. These findings suggest that the HR hippocampal mossy fibers are vulnerable to neuroadaptive alterations induced by NIC, which may be a substrate for the observed behavioral vulnerability to NIC. © 2007 Wiley-Liss, Inc. [source] Matrix-assisted laser desorption/ionization tissue profiling of secretoneurin in the nucleus accumbens shell from cocaine-sensitized ratsJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2010Joachim D. Uys Abstract Proteins in the nucleus accumbens mediate many cocaine-induced behaviors. In an effort to measure changes in nucleus accumbens protein expression as potential biomarkers for addiction, coronal tissue sections were obtained from rats that developed behavioral sensitization after daily administration of cocaine, or from daily saline-treated controls. The tissue sections were subjected to matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) profiling and tissue imaging. For profiling experiments, brain sections were manually spotted with matrix over the nucleus accumbens, a brain region known to regulate cocaine sensitization. Summed mass spectra (10 000 laser shots, grid) were acquired and spectra were aligned to reference peaks. Using bioinformatics tools, eight spectral features were found to be altered by cocaine treatment. Based on additional sequencing experiments with MALDI tandem MS and database searches of measured masses, secretoneurin (m/z 3653) was identified as having an increased expression. In addition, the distribution of m/z 3653 in the nucleus accumbens was determined by MALDI tissue imaging, and the increased expression of its precursor protein, secretogranin II, was verified by immunoblotting. Copyright © 2009 John Wiley & Sons, Ltd. [source] Neural plasticity and addiction: integrin-linked kinase and cocaine behavioral sensitizationJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Qiang Chen Abstract Behavioral sensitization of psychostimulants was accompanied by alterations in a variety of biochemical molecules in different brain regions. However, which change is actually related to drug-produced sensitization lacks of accurate clarification. In this study, we investigated the role of integrin-linked kinase (ILK) in both the induction and expression of cocaine sensitization. Conditional inhibition of ILK expression was established in the nucleus accumbens (NAc) core by microinjecting recombinant adeno-associated virus-carrying, tetracycline-on-regulated small interfering RNA which reversed the chronic cocaine-induced psychomotor sensitization, as well as the changes in protein kinase B Ser473 phosphorylation, dendritic density, and dendritic spine numbers locally. Importantly, the reversed psychomotor sensitization did not recover after cessation of the silencing for 8 days. We also demonstrated that inhibition of ILK expression pre- and during-chronic cocaine treatments blocked the induction of cocaine psychomotor sensitization and abolished the stimulant effect of cocaine on ILK expression. In contrast, inhibition of ILK expression in the NAc core has no significant effect on cocaine-induced stereotypical behaviors. This concludes that ILK is involved in cocaine sensitization with the earlier induction and later expression functioning as a kinase to regulate protein kinase B Ser473 phosphorylation and a scaffolding protein to regulate the reorganization of the NAc spine morphology. [source] Involvement of 5-HT3 receptors in the development and expression of methamphetamine-induced behavioral sensitization: 5-HT3A receptor channel and binding studyJOURNAL OF NEUROCHEMISTRY, Issue 3 2006Ji-Hoon Yoo Abstract Methamphetamine (MAP) is one of the most commonly abused drugs in Asia, and previous studies suggest that serotonin 3 receptors (5-HT3) are involved in MAP-induced locomotion and reward. However, little is known about the role of 5-HT3 receptors in MAP-induced behavioral sensitization. Here, we measured the effects of MDL 72222, a 5-HT3 antagonist, and SR 57227 A, a 5-HT3 agonist, on the development and expression of MAP-induced behavioral sensitization, and alternations of 5-HT3 receptor binding labeled with the 5-HT3 -selective antagonist, [3H]GR65630, in mice. In addition, we investigated the effects of MAP on 5-HT3A receptor channel activity in Xenopus laevis oocytes expressing 5-HT3A receptors. We found that MDL 72222 attenuated both the development and expression of behavioral sensitization to MAP (1.0 mg/kg, i.p.), and that this attenuating effect of MDL 72222 was reversed by pre-treatment with SR 57227 A. In oocytes expressing 5-HT3A receptor, MAP exhibited a dual modulation of 5-HT3A receptor channel activity, i.e. pre-treatment with a low dose of MAP (0.1 µm) enhanced 5-HT-induced inward peak current (I5-HT) but a high dose of MAP (100 µm) inhibited I5-HT. The acute administration of MDL 72222 with MAP decreased [3H]GR65630 binding versus MAP alone in the mouse striatum. Our results suggest that MDL 72222 attenuates MAP-induced behavioral sensitization via 5-HT3 receptors in the caudate putamen, and that 5-HT3 receptor antagonists like MDL 72222 have potential as novel anti-psychotic agents for the treatment of MAP dependence and psychosis. [source] The roles of calcium/calmodulin-dependent and Ras/mitogen-activated protein kinases in the development of psychostimulant-induced behavioral sensitizationJOURNAL OF NEUROCHEMISTRY, Issue 1 2003Stephanie C. Licata Abstract Although the development of behavioral sensitization to psychostimulants such as cocaine and amphetamine is confined mainly to one nucleus in the brain, the ventral tegmental area (VTA), this process is nonetheless complex, involving a complicated interplay between neurotransmitters, neuropeptides and trophic factors. In the present review we present the hypothesis that calcium-stimulated second messengers, including the calcium/calmodulin-dependent protein kinases and the Ras/mitogen-activated protein kinases, represent the major biochemical pathways whereby converging extracellular signals are integrated and amplified, resulting in the biochemical and molecular changes in dopaminergic neurons in the VTA that represent the critical neuronal correlates of the development of behavioral sensitization to psychostimulants. Moreover, given the important role of calcium-stimulated second messengers in the expression of behavioral sensitization, these signal transduction systems may represent the biochemical substrate through which the transient neurochemical changes associated with the development of behavioral sensitization are translated into the persistent neurochemical, biochemical and molecular alterations in neuronal function that underlie the long-term expression of psychostimulant-induced behavioral sensitization. [source] Increased methamphetamine-induced locomotor activity and behavioral sensitization in histamine-deficient miceJOURNAL OF NEUROCHEMISTRY, Issue 4 2002Yasuhiko Kubota Abstract We have recently suggested that the brain histamine has an inhibitory role on the behavioral effects of methamphetamine by pharmacological studies. In this study, we used the histidine decarboxylase gene knockout mice and measured the spontaneous locomotor activity, the changes of locomotion by single and repeated administrations of methamphetamine, and the contents of brain monoamines and amino acids at 1 h after a single administration of methamphetamine. In the histidine decarboxylase gene knockout mice, spontaneous locomotor activity during the dark period was significantly lower than in the wild-type mice. Interestingly, methamphetamine-induced locomotor hyperactivity and behavioral sensitization were facilitated more in the histidine decarboxylase gene knockout mice. In the neurochemical study, noradrenaline and O -phosphoserine were decreased in the midbrain of the saline-treated histidine decarboxylase gene knockout mice. On the other hand, single administration of methamphetamine decreased GABA content of the midbrain of the wild-type mice, but did not alter that of histidine decarboxylase gene knockout mice. These results suggest that the histamine neuron system plays a role as an awakening amine in concert with the noradrenaline neuron system, whereas it has an inhibitory role on the behavioral effects of methamphetamine through the interaction with the GABAergic neuron system. [source] ,-Opioid receptor knockout mice are insensitive to methamphetamine-induced behavioral sensitizationJOURNAL OF NEUROSCIENCE RESEARCH, Issue 10 2010Xine Shen Abstract Repeated administration of psychostimulants to rodents can lead to behavioral sensitization. Previous studies, using nonspecific opioid receptor (OR) antagonists, revealed that ORs were involved in modulation of behavioral sensitization to methamphetamine (METH). However, the contribution of OR subtypes remains unclear. In the present study, using ,-OR knockout mice, we examined the role of ,-OR in the development of METH sensitization. Mice received daily intraperitoneal injection of drug or saline for 7 consecutive days to initiate sensitization. To express sensitization, animals received one injection of drug (the same as for initiation) or saline on day 11. Animal locomotor activity and stereotypy were monitored during the periods of initiation and expression of sensitization. Also, the concentrations of METH and its active metabolite amphetamine in the blood were measured after single and repeated administrations of METH. METH promoted significant locomotor hyperactivity at low doses and stereotyped behaviors at relative high doses (2.5 mg/kg and above). Repeated administration of METH led to the initiation and expression of behavioral sensitization in wild-type mice. METH-induced behavioral responses were attenuated in the ,-OR knockout mice. Haloperidol (a dopamine receptor antagonist) showed a more potent effect in counteracting METH-induced stereotypy in the ,-OR knockout mice. Saline did not induce behavioral sensitization in either genotype. No significant difference was observed in disposition of METH and amphetamine between the two genotypes. Our study indicated that the ,-opioid system is involved in modulating the development of behavioral sensitization to METH. © 2010 Wiley-Liss, Inc. [source] Proopiomelanocortin Peptides Are Not Essential for Development of Ethanol-Induced Behavioral SensitizationALCOHOLISM, Issue 7 2009Amanda L. Sharpe Background:, Behavioral sensitization is a result of neuroadaptation to repeated drug administration and is hypothesized to reflect an increased susceptibility to drug abuse. Proopiomelanocortin (POMC) derived peptides including ,-endorphin and ,-melanocyte stimulating hormone have been implicated in development of behavioral sensitization and the reinforcing effects of alcohol and other drugs of abuse. This study used a genetically engineered mouse strain that is deficient for neural POMC to directly determine if any POMC peptides are necessary for the development of ethanol-induced locomotor sensitization. Methods:, Adult female mice deficient for POMC in neurons only (Pomc,/,Tg/Tg, KO) and wildtype (Pomc+/+Tg/Tg, WT) littermates were injected once daily with either saline or ethanol (i.p.) for 12 to 13 days. On ethanol test day (day 13 or 14) all mice from both treatment groups received an i.p. injection of ethanol immediately before a 15-minute analysis of locomotor activity. Blood ethanol concentration (BEC) was measured on ethanol test day immediately following the test session. Baseline locomotor activity was measured for 15 minutes after a saline injection 2 days later in both groups. Results:, There was no significant difference in BEC between genotypes (WT = 2.11 ± 0.06; KO = 2.03 ± 0.08 mg/ml). Both WT and nPOMC-deficient mice treated repeatedly with ethanol demonstrated a significant increase in locomotor activity on test day when compared to repeated saline-treated counterparts. In addition, mice of both genotypes in the repeated saline groups showed a significant locomotor stimulant response to acute ethanol injection. Conclusions:, Central POMC peptides are not required for either the acute locomotor stimulatory effect of ethanol or the development of ethanol-induced locomotor sensitization. While these peptides may modulate other ethanol-associated behaviors, they are not essential for development of behavioral sensitization. [source] Behavioral Consequences of Repeated Nicotine During Adolescence in Alcohol-Preferring AA and Alcohol-Avoiding ANA RatsALCOHOLISM, Issue 2 2009Heidi Kemppainen Background:, Epidemiological studies suggest that exposure to nicotine at adolescent age is associated with increased potential to use alcohol and that genetic predisposition may further increase the risk. The present study addressed adolescent vulnerability to repeated nicotine exposure and its influence on subsequent ethanol self-administration by investigating interactions between nicotine-induced behavioral sensitization and voluntary ethanol consumption in alcohol preferring AA (Alko Alcohol) and alcohol nonpreferring ANA (Alko Non-Alcohol) rat lines selected for differential ethanol intake. Methods:, Adolescent and adult rats received 10 injections of nicotine (0.5 mg/kg s.c.), given every second day from postnatal day (Pnd) 27 and 75, respectively. Nicotine-induced (0.5 mg/kg) locomotor activity was measured acutely after the first injection, and after the repeated treatment with nicotine on Pnds 52 and 86 in the adolescent groups and on Pnd 99 in the adult groups. After this, acquisition of voluntary ethanol (10% v/v) consumption as well as nicotine-induced (0.5 mg/kg) ethanol intake was measured in the AA rats. Results:, Adolescent AA rats were more sensitive than adolescent ANA rats to the locomotor effects of nicotine. They were also stimulated more than adult AA rats, but such a difference was not found among ANA rats. Adolescent and adult rats did not differ in their susceptibility to nicotine-induced behavioral sensitization. Genetic predisposition to ethanol self-administration did not interact with development of behavioral sensitization in either adolescents or adults. Acquisition of ethanol intake was enhanced in the adolescent groups relative to the adult groups in a manner that was independent of the nicotine treatment. An increase in ethanol intake was found after challenging animals with nicotine, and this effect was enhanced in the nicotine-treated adolescent group. Conclusions:, These findings provide no or little support for the views that adolescent animals are more sensitive to the neurobehavioral effects of repeated exposure to nicotine and that exposure to nicotine in adolescence may contribute to enhanced vulnerability to ethanol abuse. Furthermore, genetic predisposition to high or low ethanol self-administration does not seem to be a factor that influences individual vulnerability to the neurobehavioral effects of repeated administration of nicotine. [source] | ||||||||||