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Conditioned Place Preference (conditioned + place_preference)
Selected AbstractsDecreased Sensitivity to Ethanol Reward in Adolescent Mice as Measured by Conditioned Place PreferenceALCOHOLISM, Issue 7 2009Shelly D. Dickinson Background:, Many preclinical studies have demonstrated age-related differential sensitivity to various effects of ethanol between adolescent and adult animals. However, published data addressing possible differences in ethanol's motivational effects are sparse, particularly in mice. The present study examined age-related differences in the conditioned rewarding effects of ethanol in DBA/2J mice. Methods:, In the first experiment an unbiased place conditioning procedure was used to determine the rewarding effects of 2 g/kg ethanol in adult and adolescent DBA/2J mice. In a subsequent place conditioning experiment, the effects of 2 and 4 g/kg were assessed in adolescent mice. Results:, Adolescents demonstrated a place preference with the high dose of 4 g/kg but not with a more moderate dose of 2 g/kg. In contrast, 2 g/kg was sufficient to produce place preference in adult mice. Conclusions:, Adolescents are less sensitive than adults to the rewarding effects of ethanol but can experience reward with high doses. These results extend the current literature on ethanol's effects in adolescent animals. [source] Chronic social stress in adolescence influenced both amphetamine conditioned place preference and locomotor sensitizationDEVELOPMENTAL PSYCHOBIOLOGY, Issue 5 2008I. Z. Mathews Abstract We previously reported that chronic social stress (SS) in adolescence, but not in adulthood, increased the locomotor-activating effects of nicotine in females, and not males, when tested in adulthood. However, SS rats had decreased locomotor response to nicotine when tested in adolescence. Here, we investigated age-related changes in the effects of SS on both conditioned place preference (CPP) and locomotor sensitization to amphetamine. In the CPP experiment, SS females tested in adolescence had increased preference for the 1.0 mg/kg dose of amphetamine, whereas SS rats of both sexes showed a decrease in CPP for the 0.5 mg/kg dose when tested as adults. Irrespective of time of testing, SS males and females had enhanced locomotor sensitization compared to controls. Thus, adolescent SS produced both immediate and enduring effects on behavioral responses to amphetamine, likely by altering the development of the mesocorticolimbic dopamine system, which holds implications for vulnerability to addiction. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 451,459, 2008. [source] PRECLINICAL STUDY: Proteomic analysis of methamphetamine-induced reinforcement processes within the mesolimbic dopamine systemADDICTION BIOLOGY, Issue 3-4 2008Moon Hee Yang ABSTRACT Methamphetamine (MAP) is a commonly used, addictive drug, and a powerful stimulant that dramatically affects the central nervous system. In this study, we used the conditioned place preference (CPP) paradigm in order to study the reinforcing properties of MAP and the herewith associated changes in proteins within the mesolimbic dopamine system. A CPP was induced by MAP after three intermittent intraperitoneal injections (1 mg/kg) in rats and protein profiles in the nucleus accumbens, striatum, prefrontal cortex, cingulate cortex and hippocampus were compared with a saline-treated control group. In addition, a group of animals was run through extinction and protein profiles were compared with a non-extinguished group. Protein screening was conducted using two-dimensional electrophoresis analysis which identified 27 proteins in the group that showed MAP-induced CPP. Some of the proteins were confirmed by Western lot analysis. Identified proteins had functions related to the cytoskeleton, transport/endocytosis or exocytosis (e.g. profilin-2 and syntaxin-binding protein), and signal transduction, among others. [source] REVIEW: Behavioural assessment of drug reinforcement and addictive features in rodents: an overviewADDICTION BIOLOGY, Issue 1 2006Carles Sanchis-Segura ABSTRACT Some psychoactive drugs are abused because of their ability to act as reinforcers. As a consequence behavioural patterns (such as drug-seeking/drug-taking behaviours) are promoted that ensure further drug consumption. After prolonged drug self-administration, some individuals lose control over their behaviour so that these drug-seeking/taking behaviours become compulsive, pervading almost all life activities and precipitating the loss of social compatibility. Thus, the syndrome of addictive behaviour is qualitatively different from controlled drug consumption. Drug-induced reinforcement can be assessed directly in laboratory animals by either operant or non-operant self-administration methods, by classical conditioning-based paradigms such as conditioned place preference or sign tracking, by facilitation of intracranial electric self-stimulation, or, alternatively by drug-induced memory enhancement. In contrast, addiction cannot be modelled in animals, at least as a whole, within the constraints of the laboratory. However, various procedures have been proposed as possible rodent analogues of addiction's major elements including compulsive drug seeking, relapse, loss of control/impulsivity, and continued drug consumption despite negative consequences. This review provides an extensive overview and a critical evaluation of the methods currently used for studying drug-induced reinforcement as well as specific features of addictive behaviour. In addition, comic strips that illustrate behavioural methods used in the drug abuse field are provided given for free download under http://www.zi-mannheim/psychopharmacology.de [source] Effects of MPEP on expression of food-, MDMA- or amphetamine-conditioned place preference in ratsADDICTION BIOLOGY, Issue 3 2005Volker Herzig Recent studies have revealed the effectiveness of 2-methyl-6-(phenylethynyl)pyridine (MPEP), a highly selective antagonist of metabotropic glutamate receptors subtype 5 (mGluR5), in conditioned drug reward. In a previous study we showed that MPEP blocks expression of context-conditioned morphine- but not cocaine reward in the rat. The present study now examines the effectiveness of MPEP in the expression of context-conditioned food, MDMA (,ecstasy?) or amphetamine reward. Therefore, three groups of rats were conditioned either to food, MDMA or amphetamine in the conditioned place preference (CPP) paradigm. After conditioning, CPP expression and locomotion were determined simultaneously in the presence and absence of the respective reward (i.e. food or drug), or after application of 50?mg/kg MPEP (the dose that was most effective in reducing morphine CPP expression in our previous study). As a result, MPEP reduced locomotion in all groups. Furthermore, only expression of amphetamine CPP was inhibited by MPEP, while expression of food and MDMA CPP was not affected, suggesting that the MPEP-induced inhibition of amphetamine CPP expression was not causally linked to the reduction of locomotion. Overall, we conclude that MPEP reduces expression of context-conditioned amphetamine but not MDMA or food reward. [source] Melatonin enhances the rewarding properties of morphine: involvement of the nitric oxidergic pathwayJOURNAL OF PINEAL RESEARCH, Issue 4 2007Noushin Yahyavi-Firouz-Abadi Abstract:, Melatonin has different interactions with opioids including the enhancement of the analgesic effects of morphine and also reversal of tolerance and dependence to morphine. The present study assessed the effect of melatonin on morphine reward in mice using a conditioned place preference (CPP) paradigm. Our data showed that subcutaneous administration of morphine (1,7.5 mg/kg) significantly increased the time spent in the drug-paired compartment in a dose-dependent manner. Intraperitoneal (i.p.) administration of melatonin (1,40 mg/kg) alone did not induce either CPP or conditioned place aversion (CPA), while the combination of melatonin (5,20 mg/kg) and sub-effective dose of morphine (0.5 mg/kg) led to rewarding effect. We further investigated the involvement of the nitric oxidergic pathway in the enhancing effect of melatonin on morphine CPP, by a general nitric oxide synthase inhibitor, NG -nitro- l -arginine methyl ester (l -NAME). l -NAME (1 and 5 mg/kg, i.p.) alone or in combination with morphine (0.5 mg/kg) did not show any significant CPP or CPA. Co-administration of l -NAME (5 mg/kg) with an ineffective combination of melatonin (1 mg/kg) plus morphine (0.5 mg/kg) produced significant CPP that may imply the similarity of action of melatonin and l -NAME and involvement of the nitric oxidergic pathway in this regard. Our results indicate that pretreatment of animals with melatonin enhances the rewarding properties of morphine via a mechanism which may involve the nitric oxidergic pathway. [source] Suppression of Heavy Drinking and Alcohol Seeking by a Selective ALDH-2 InhibitorALCOHOLISM, Issue 11 2009Maria P. Arolfo Background:, Inherited human aldehyde dehydrogenase 2 (ALDH-2) deficiency reduces the risk for alcoholism. Kudzu plants and extracts have been used for 1,000 years in traditional Chinese medicine to treat alcoholism. Kudzu contains daidzin, which inhibits ALDH-2 and suppresses heavy drinking in rodents. Decreased drinking due to ALDH-2 inhibition is attributed to aversive properties of acetaldehyde accumulated during alcohol consumption. However, daidzin can reduce drinking in some rodents without necessarily increasing acetaldehyde. Therefore, a selective ALDH-2 inhibitor might affect other metabolic factors involved in regulating drinking. Methods:, Aldehyde dehydrogenase 2 inhibitors were synthesized based on the co-crystal structure of ALDH-2 and daidzin. We tested the efficacy of a highly selective reversible ALDH-2 inhibitor, CVT-10216, in models of moderate and high alcohol drinking rats. We studied 2-bottle choice and deprivation-induced drinking paradigms in Fawn Hooded (FH) rats, operant self-administration in Long Evans (LE), FH, and inbred P (iP) rats and in cue-induced reinstatement in iP rats. We also assayed blood acetaldehyde levels as well as dopamine (DA) release in the nucleus accumbens (NAc) and tested possible rewarding/aversive effects of the inhibitor in a conditioned place preference (CPP) paradigm. Results:, CVT-10216 increases acetaldehyde after alcohol gavage and inhibits 2-bottle choice alcohol intake in heavy drinking rodents, including deprivation-induced drinking. Moreover, CVT-10216 also prevents operant self-administration and eliminates cue-induced reinstatement of alcohol seeking even when alcohol is not available (i.e., no acetaldehyde). Alcohol stimulates DA release in the NAc, which is thought to contribute to increased drinking and relapse in alcoholism. CVT-10216 prevents alcohol-induced increases in NAc DA without changing basal levels. CVT-10216 does not show rewarding or aversive properties in the CPP paradigm at therapeutic doses. Conclusion:, Our findings suggest that selective reversible ALDH-2 inhibitors may have therapeutic potential to reduce excessive drinking and to suppress relapse in abstinent alcoholics. [source] Ethanol-Related Behaviors in Serotonin Transporter Knockout MiceALCOHOLISM, Issue 12 2006Janel M. Boyce-Rustay Background: Increasing evidence supports a role for 5-hydroxytryptamine (5-HT) and the 5-HT transporter (5-HTT) in modulating the neural and behavioral actions of ethanol (EtOH) and other drugs of abuse. Methods: We used a 5-HTT knockout (KO) mouse model to further study this relationship. 5-Hydroxytryptamine transporter KO mice were tested for the sedative/hypnotic, hypothermia-inducing, motor-incoordinating (via accelerating rotarod), and depression-related (via tail suspension test) effects of acute EtOH administration. Reward-related effects of EtOH were assessed in 5-HTT KO mice using the conditioned place preference (CPP) paradigm. 5-Hydroxytryptamine transporter KO mice were tested for voluntary consumption of EtOH in a modified 2-bottle choice test that measured the temporal organization of drinking over the circadian cycle via "lickometers." Results: Replicating previous findings, 5-HTT KO mice exhibited significantly increased sensitivity to EtOH-induced sedation/hypnosis relative to wild-type controls. Additionally, 5-HTT KO mice showed motor-coordination deficits at baseline and in response to EtOH. Hypothermic, pro-depressive,like, and reward-related effects of EtOH were no different across genotypes. Gross EtOH consumption was modestly reduced in 5-HTT KO mice, due to significantly lesser consumption during the peak period of drinking in the early dark phase. Conclusions: Data extend the finding that loss of 5-HTT gene function alters certain neural and behavioral effects of EtOH, with implications for better understanding the pathophysiology and treatment of alcoholism. [source] Helplessness in the Tail Suspension Test Is Associated with an Increase in Ethanol Intake and Its Rewarding Effect in Female MiceALCOHOLISM, Issue 3 2005Yann Pelloux Background: Depression is frequently observed in drug abusers. However, depression may be a primary factor of predisposition to drug abuse or a consequence of drug abuse. The aim of this study was to analyze the influence of a preexisting depressive-like state/helplessness on subsequent alcohol responsiveness in mice. Methods: Male and female CD1 mice were selected according to their immobility time in the tail suspension test, and only mice with "high immobility" and "low immobility" time were retained. Using a two-bottle free-choice paradigm, these mice were given continuous access to tap water or solutions of ethanol (3,20% v/v), quinine (12.5,50 mg/liter), or sucrose (1,4% w/v). In female mice, rewarding and aversive effects of ethanol (1.5 and 3 g/kg, intraperitoneally) were also investigated using the conditioned place preference and the conditioned taste aversion paradigms. Results: Female mice were more immobile and drank more ethanol than male mice. No striking sex difference was observed in quinine consumption. Sucrose intake was higher in female than in male mice, whatever the solution concentration. At the 4% concentrated solution, a sucrose-induced increase in daily fluid intake was observed only in female mice. Female mice with high immobility time (HI) consumed more ethanol at the highest concentration than female mice with low immobility time (LI), whereas no difference was observed between HI and LI male mice. Moreover, whereas LI female mice failed to express place conditioning induced by the 3-g/kg dose of ethanol, HI female mice were strongly responsive to the rewarding effect of this high ethanol dose. Ethanol dose-dependently induced a conditioned taste aversion with a similar magnitude in both LI and HI female mice. Conclusions: The findings indicate that female CD1 mice tend to drink greater amounts of ethanol or sucrose solutions than male CD1 mice, suggesting that female mice may be a better model of excessive alcohol intake. Furthermore, no relationship was found between immobility scores and ethanol consumption in male mice. On the contrary, within female mice, HI mice consumed higher amounts of ethanol than LI mice probably because they experienced greater rewarding effects of ethanol. The present results support the hypothesis that depressive-like responses may predispose to ethanol abuse in female mice. [source] Behavioural and biochemical evidence for interactions between ,9-tetrahydrocannabinol and nicotineBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2002Emmanuel Valjent Behavioural and pharmacological effects of ,9-tetrahydrocannabinol (THC) and nicotine are well known. However, the possible interactions between these two drugs of abuse remain unclear in spite of the current association of cannabis and tobacco in humans. The present study was designed to analyse the consequences of nicotine administration on THC-induced acute behavioural and biochemical responses, tolerance and physical dependence. Nicotine strongly facilitated hypothermia, antinociception and hypolocomotion induced by the acute administration of THC. Furthermore, the co-administration of sub-threshold doses of THC and nicotine produced an anxiolytic-like response in the light,dark box and in the open-field test as well as a significant conditioned place preference. Animals co-treated with nicotine and THC displayed an attenuation in THC tolerance and an enhancement in the somatic expression of cannabinoid antagonist-precipitated THC withdrawal. THC and nicotine administration induced c-Fos expression in several brain structures. Co-administration of both compounds enhanced c-Fos expression in the shell of the nucleus accumbens, central and basolateral nucleus of the amygdala, dorso-lateral bed nucleus of the stria terminalis, cingular and piriform cortex, and paraventricular nucleus of the hypothalamus. These results clearly demonstrate the existence of a functional interaction between THC and nicotine. The facilitation of THC-induced acute pharmacological and biochemical responses, tolerance and physical dependence by nicotine could play an important role in the development of addictive processes. British Journal of Pharmacology (2002) 135, 564,578; doi:10.1038/sj.bjp.0704479 [source] | |||||||||||||