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Cocaine use results in anhedonia during withdrawal, but it is not clear how this emotional state interacts with an individual's vulnerability for addiction. Rats selectively bred for high (HiS) or low (LoS) saccharin intake are a well-established model of drug abuse vulnerability, with HiS rats being more likely to consume sweets and drugs of abuse such as cocaine and heroin (Carroll et al., 2002) than LoS rats. This study examined whether the motivational consequences of cocaine withdrawal are differentially expressed in HiS and LoS rats. HiS and LoS rats were trained to respond for a sucrose reward on a progressive ratio (PR) schedule of reinforcement and breakpoints were measured during and after chronic, continuous exposure to cocaine (30 mg/kg/day). Cocaine, but not saline, treatment resulted in lower breakpoints for sucrose during withdrawal in LoS rats only. These results suggest anhedonia during withdrawal is more pronounced in the less vulnerable LoS rats. Fewer motivational deficits during withdrawal may contribute to greater drug vulnerability in the HiS line., (Published by Elsevier Inc.)

Rationale: Adolescence marks a period of increased vulnerability to the development of substance use disorders. High sweet preference is a genetically mediated behavioral trait that also predicts vulnerability to substances of abuse. Previous research has shown that while adolescent rats selectively bred for high (HiS) saccharin intake acquire cocaine self-administration at the same rate as adult HiS rats, adolescent rats bred for low saccharin intake (LoS) acquire cocaine self-administration faster than adult LoS rats. Objectives: This study was conducted to investigate the interaction of the addiction vulnerability factors of peri-adolescence and saccharin preference on cocaine intake using an animal model of escalation of cocaine consumption over 6-h/day sessions. Methods: Peri -adolescent and adult HiS and LoS female rats self-administered i.v. cocaine (0.4 mg/kg/inf) during short-access (2-h/day) sessions for 2 days. Next, a long-access (6-h/day) period (LgA) commenced and lasted 16 days. Following LgA, session length was returned to 2-h/day for a second short access phase. Results: LoS peri-adolescent rats escalated cocaine intake over the LgA period and consumed more drug than LoS adult rats; however, peri-adolescent and adult HiS rats consumed similar amounts of cocaine during this period. Additionally, adult HiS rats self-administered more cocaine than adult LoS rats during the LgA period, while there was no phenotypic difference between the rat lines during peri-adolescence for the LgA period. During the first short-access phase, peri-adolescent rats self-administered more cocaine than adult rats. Conclusions: These results emphasize the importance of adolescent drug abuse prevention by illustrating that phenotypic protection from addiction may not be expressed until adulthood. [ABSTRACT FROM AUTHOR]

Abstract: Sweet preference and impulsivity are predictors of cocaine self-administration; however, no research has been conducted to investigate neuronal activation in key brain reward areas after first time exposure to cocaine in rats that differ in their propensity for cocaine-seeking and -taking behavior. In this study we used rats that had been selectively bred for high vs. low saccharin intake and rats selected for high vs. low impulsivity for food. The goal of this study was to investigate whether there are differences of c-Fos reactivity between high and low phenotypes and determine whether these differences are similar between the two animal models. A group of rats was bred for high or low saccharin intake. Another group of rats was selected as high or low impulsive based on performance in a delay-discounting task. Subsequently, rats were given an acute injection of cocaine or saline and then c-Fos expression was observed and analyzed in several brain regions. The low reward-seeking phenotypes showed higher cocaine-induced c-Fos expression in several of these regions. Low saccharin preferring rats showed higher cocaine-induced c-Fos expression in the nucleus accumbens shell, and low impulsive rats showed higher cocaine-induced c-Fos expression in the orbitofrontal cortex and cingulate gyrus 1 area. In addition, both low impulsive and low saccharin rats had higher cocaine-induced c-Fos in the dorsal medial and dorsal lateral caudate putamen. The results indicate that individual differences in neuronal reactivity exist prior to chronic exposure to drugs of abuse. Furthermore, similar differences between the two animal models may be indicative of a common mechanism underlying vulnerability to drugs of abuse. [Copyright &y& Elsevier]

Abstract: Background: Environmental factors such as early drug exposure influence drug abuse vulnerability, and evidence also suggests that drug abuse is highly heritable. The purpose of the present study was to determine whether environmental and genetic factors interact to produce additive drug abuse vulnerability. Methods: An animal model of relapse was used to examine the effects of adolescent nicotine exposure on adult cocaine seeking in rats bred for high (HiS) and low (LoS) saccharin intake. Rats from HiS and LoS progenitor lines received s.c. injections of nicotine for 10 days (postnatal days 22–31). Rats were then allowed to reach adulthood and were trained to lever press for cocaine infusions. During each self-administration session, the house light (HL) was illuminated and each lever press activated a set of lights adjacent to the lever (LL). Following cocaine self-administration, the HL and LL were deactivated, cocaine solutions were replaced with saline, and rats extinguished lever pressing. Subsequently, rats were tested under a multi-component reinstatement procedure consisting of: (1) cue-induced reinstatement with LL alone and the HL presented alone, (2) cocaine-induced reinstatement without LL and HL present, (3) and cocaine-induced reinstatement with LL present. Results: The results indicated that adolescent nicotine exposure sensitized the reinstatement of cocaine seeking during adulthood in HiS (but not LoS) rats when lever pressing resulted in LL cue presentations. In addition, following administration of the cocaine priming injection, rats exposed to nicotine (vs. saline) during adolescence (LoS and HiS) engaged in more cocaine seeking under the cocaine-primed reinstatement condition when lever pressing illuminated the LL. Conclusion: These results suggest that drug abuse vulnerability may be a function of early life exposure to drugs of abuse in addition to genetic influences. [Copyright &y& Elsevier]