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Operant Ethanol Self-administration (operant + ethanol_self-administration)
Selected AbstractsThe Dopamine Response in the Nucleus Accumbens Core,Shell Border Differs From That in the Core and Shell During Operant Ethanol Self-AdministrationALCOHOLISM, Issue 8 2009Elaina C. Howard Background:, Ethanol self-administration has been shown to increase dopamine in the nucleus accumbens; however, dopamine levels in the accumbal subregions (core, shell, and core,shell border) have not yet been measured separately in this paradigm. This study was designed to determine if dopamine responses during operant ethanol self-administration are similar in the core, core,shell border, and shell, particularly during transfer from the home cage to the operant chamber and during consumption of the drinking solution. Methods:, Six groups of male Long,Evans rats were trained to lever-press for either 10% sucrose (10S) or 10% sucrose + 10% ethanol (10S10E) (with a guide cannula above the core, core,shell border, or shell of the accumbens). On experiment day, 5-minute microdialysis samples were collected from the core, core,shell border, or shell before, during, and after drinking. Dopamine and ethanol concentrations were analyzed in these samples. Results:, A significant increase in dopamine occurred during transfer of the rats from the home cage into the operant chamber in all 6 groups, with those trained to drink 10S10E exhibiting a significantly higher increase than those trained to drink 10S in the core and shell. No significant increases were observed during drinking of either solution in the core or shell. A significant increase in dopamine was observed during consumption of ethanol in the core,shell border. Conclusions:, We conclude that dopamine responses to operant ethanol self-administration are subregion specific. After operant training, accumbal dopamine responses in the core and shell occur when cues that predict ethanol availability are presented and not when the reinforcer is consumed. However, core,shell border dopamine responses occur at the time of the cue and consumption of the reinforcer. [source] Early Social Isolation in Male Long-Evans Rats Alters Both Appetitive and Consummatory Behaviors Expressed During Operant Ethanol Self-AdministrationALCOHOLISM, Issue 2 2009Brian A. McCool Background:, Postweaning social isolation in rats produces profound and long-lasting cognitive and behavioral deficits in adult animals. Importantly, this housing manipulation alters sensitivity to a number of drugs of abuse including ethanol. However, most studies with ethanol have utilized continuous or limited home-cage access to examine interactions between juvenile social experience and drinking. More recently, social isolation was shown to increased ethanol responding in a "dipper" model of self-administration (Deehan et al., 2007). In the current study, we utilize a "sipper" operant self-administration model to distinguish the effects of isolation rearing on ethanol seeking- and drinking-related behaviors. Methods:, Postweaning juvenile male Long-Evans rats were placed into 2 housing groups for 6 weeks: one group consisted of individually housed animals; the second group was housed 4 animals per cage. Following the isolation period, anxiety-like behavior was assessed to confirm the efficacy of the isolation procedure. In some animals, ethanol drinking in the home cage was assessed using a continuous access, 2-bottle choice paradigm. All animals were then individually housed and trained to lever-press for a sipper tube containing either an ethanol solution or a sucrose solution. Results:, Postweaning social isolation increased the expression of anxiety-like behavior in the elevated plus maze but not the light-dark box. Ethanol consumption was also increased during continuous home-cage access with the 2-bottle choice paradigm. During operant self-administration, isolation housing increased the response rate and increased ethanol consumption but did not alter responding for or consumption of sucrose. The housing manipulation did not change the total number of lever responses during extinction sessions. Paired-pulse inhibition deficits that are characteristic of juvenile isolation remained intact after prolonged experience with sucrose self-administration. Discussion:, The effects of postweaning social isolation on ethanol drinking in the home cage are also manifest during operant self-administration. Importantly, these alterations in adult operant self-administration are ethanol-specific. [source] The acute anti-craving effect of acamprosate in alcohol-preferring rats is associated with modulation of the mesolimbic dopamine systemADDICTION BIOLOGY, Issue 3 2005Michael Cowen Acamprosate (Campral ?) is a drug used clinically for the treatment of alcoholism. In order to examine further the time-course and mechanism of action of acamprosate, the effect of acute and repeated acamprosate administration was examined on (i) operant ethanol self-administration and (ii) voluntary home cage ethanol consumption by alcohol-preferring Fawn-Hooded, iP and Alko Alcohol (AA) rats. Acutely, acamprosate was shown to cause a significant decrease in operant ethanol self-administration by Fawn-Hooded and alcohol-preferring iP rats in part by decreasing the motivational relevance of a specific ethanol cue; however, repeated injection of acamprosate led to tolerance to this effect. Voluntary alcohol consumption in the home cage in Fawn-Hooded and AA rats was also reduced by an acute acamprosate injection; however, again tolerance developed to repeated injections. In a separate experiment, the effect of acamprosate on markers of the dopaminergic system was examined. Interestingly, acute acamprosate was also shown to cause increased dopamine transporter density and decreased dopamine D2-like receptor density within the nucleus accumbens but not in the caudate-putamen, suggesting a link between the decreased motivational salience of the ethanol cue and altered dopaminergic signalling within the nucleus accumbens. With repeated injections of acamprosate, markers of the dopaminergic system returned to steady state levels with a similar temporal profile to the development of tolerance in the behavioural studies. Along with previous studies, our findings indicate that acamprosate modulates the mesolimbic dopaminergic system and may thereby decrease ethanol reinforcement processes; however, these effects undergo tolerance in alcohol-preferring rats and may in part explain the fact why some subjects are non-responders to chronic acamprosate treatment. [source] Reduced operant ethanol self-administration and in vivo mesolimbic dopamine responses to ethanol inPKC,-deficient miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2000M. Foster Olive Abstract There is increasing evidence that individual protein kinase C (PKC) isozymes mediate specific effects of ethanol on the nervous system. In addition, multiple lines of evidence suggest that the mesoaccumbens dopamine reward system is critically involved in the rewarding and reinforcing effects of ethanol. Yet little is known about the role of individual PKC isozymes in ethanol reinforcement processes or in regulation of mesolimbic systems. In this study, we report that mice lacking the epsilon isoform of PKC (PKC,) show reduced operant ethanol self-administration and an absence of ethanol-induced increase in extracellular dopamine levels in the nucleus accumbens. PKC, null mice exhibited a 53% decrease in alcohol-reinforced operant responses under basal conditions, as well as following ethanol deprivation. Behavioural analysis revealed that while both genotypes had the same number of drinking bouts following deprivation, PKC, null mice demonstrated a 61% reduction in number of ethanol reinforcers per bout and a 57% reduction in ethanol-reinforced response rate. In vivo microdialysis experiments showed that, in contrast to wild-type mice, PKC, null mice exhibited no change in extracellular levels of dopamine in the nucleus accumbens following acute administration of ethanol (1 and 2 g/kg i.p.), while mesolimbic dopamine responses to cocaine (20 mg/kg i.p.) or high potassium (100 m m) in these mice were comparable with that of wild-types. These data provide further evidence that increases in extracellular mesolimbic dopamine levels contribute to the reinforcing effects of ethanol, and indicate that pharmacological agents inhibiting PKC, may be useful in the treatment of alcohol dependence. [source] The Dopamine Response in the Nucleus Accumbens Core,Shell Border Differs From That in the Core and Shell During Operant Ethanol Self-AdministrationALCOHOLISM, Issue 8 2009Elaina C. Howard Background:, Ethanol self-administration has been shown to increase dopamine in the nucleus accumbens; however, dopamine levels in the accumbal subregions (core, shell, and core,shell border) have not yet been measured separately in this paradigm. This study was designed to determine if dopamine responses during operant ethanol self-administration are similar in the core, core,shell border, and shell, particularly during transfer from the home cage to the operant chamber and during consumption of the drinking solution. Methods:, Six groups of male Long,Evans rats were trained to lever-press for either 10% sucrose (10S) or 10% sucrose + 10% ethanol (10S10E) (with a guide cannula above the core, core,shell border, or shell of the accumbens). On experiment day, 5-minute microdialysis samples were collected from the core, core,shell border, or shell before, during, and after drinking. Dopamine and ethanol concentrations were analyzed in these samples. Results:, A significant increase in dopamine occurred during transfer of the rats from the home cage into the operant chamber in all 6 groups, with those trained to drink 10S10E exhibiting a significantly higher increase than those trained to drink 10S in the core and shell. No significant increases were observed during drinking of either solution in the core or shell. A significant increase in dopamine was observed during consumption of ethanol in the core,shell border. Conclusions:, We conclude that dopamine responses to operant ethanol self-administration are subregion specific. After operant training, accumbal dopamine responses in the core and shell occur when cues that predict ethanol availability are presented and not when the reinforcer is consumed. However, core,shell border dopamine responses occur at the time of the cue and consumption of the reinforcer. [source] | ||||||||||