Effects of exposure to polychlorinated biphenyls during different periods of development on ethanol consumption by male and female rats.

In two experiments, male and female Sprague-Dawley rats were exposed to Polychlorinated Biphenyls (PCBs) to assess the effect PCBs, an estrogenic endocrine disrupting chemical (EEDC), would have on the voluntary consumption of alcohol. There are several EEDCs in our food that are known to increase estrogen in adolescent females. Our objective was to assess the effect that increasing estrogen, by adding the EEDC PCBs would have on volitional intake of alcohol. In Experiment 1, pregnant dams were exposed from gestational days 5-19 to a 1:1 mixture of Aroclor 1254/1260. In Experiment 2, lactating females were exposed to the same dose of 1254:1260 from postnatal days 1-21. In both experiments, a fade-in procedure was used to gradually introduce the rats to the taste of alcohol. At the end of the fade-in series all animals were given limited access (1 h/day) to a water/alcohol solution. We found that females exposed to PCBs, at two developmental periods, consumed significantly more alcohol than unexposed females and exposed and unexposed males. Results of the experiments are discussed in terms of how PCB exposure can disrupt endocrine processes (e.g., estrogenic endocrine disrupting chemicals, EEDC) that increase estrogen in females, thereby leading to increased alcohol consumption. Thus, the present findings suggest that EEDCs, such as PCBs, could contribute to the increase abuse of alcohol in adolescent females.

Environmental enrichment induces early heroin abstinence in an animal conflict model.

RATIONALE AND OBJECTIVES: Heroin addiction is a significant health and societal problem for which there is no highly effective long-term behavioral or pharmacological treatment. Therefore, strategies that support heroin abstinence should be a primary focus of heroin treatment research. To this end, the current study used an animal conflict model that captures the aversive consequences of drug seeking (as are typical in humans, e.g., incarceration and job loss) to induce abstinence. Using this abstinence model, we examined the capacity of environmental enrichment (EE) to facilitate abstinence in heroin seeking rats. METHODS: The procedure consisted of two phases: drug self-administration (phase 1) and electric barrier application (phase 2) that resulted in abstinence. For phase 1, male rats were trained to self-administer intravenous heroin under a fixed-ratio schedule of reinforcement. After self-administration was acquired, animals were housed either in EE or standard cages (non-EE control). During abstinence in phase 2, the electric barrier was introduced in the operant conditioning chambers by electrifying the floor area near the levers. RESULTS: We found that EE rats achieved abstinence (zero active lever presses for 3 consecutive sessions) in significantly fewer sessions than NEE rats. Further, EE rats abstained at significantly lower electric currents than NEE rats. CONCLUSIONS: EE facilitated abstinence in the conflict model. The current use of the abstinence-conflict model to investigate EE as a behavioral strategy to facilitate abstinence will help in the development of effective treatments for human addicts by bringing together the positive consequences of abstinent behavior in an enriched environment with the aversive consequences of drug seeking.

Drug abstinence: exploring animal models and behavioral treatment strategies.

BACKGROUND AND RATIONALE: An enormous amount of resources has been devoted to the development of pharmacotherapies for drug addiction, with relatively little or no long-term success reported. The current review argues that a successful drug addiction treatment program will likely be one that focuses on both the neural mechanisms and the environmental contingencies that mediate drug use. Further, because the neural mechanisms and environmental factors that support abstinence in humans are similar in laboratory animals, several animal models of abstinence and relapse have been developed. Thus, this review also compares the similarities in the mechanisms that lead to abstinence between animals and humans. OBJECTIVE: We evaluate the construct and face validities of the behavioral strategies that help support human drug abstinence. Further, we crucially evaluate animal models by assessing their validity and utility in addressing human behavior that leads to long-term abstinence. CONCLUSIONS: We found that the behavioral strategies with the greatest likelihood of supporting long-term abstinence are those that are carried out in drug addicts' natural setting(s) and while drug is readily available. Further, the behavioral strategies that may be most successful in supporting abstinence in humans are those that employ both positive consequences for abstinent related behavior and negative consequences for continued drug seeking or taking. Moreover, the animal models of abstinence and relapse that more closely represent the factors that support long-term abstinence in humans are those that limit their use of extinction or forced abstinence and present negative consequences for drug seeking and taking.

Cue-induced resumption of heroin and cocaine seeking in rats using a conflict model of abstinence and relapse.

RATIONALE AND OBJECTIVES: Most animal research on drug relapse involves the reinstatement model where abstinence is a result of drug removal (extinction). However, abstinence in humans often results from the aversive consequences that accompany drug seeking (conflict situation). This study was aimed at using a conflict-based animal model of abstinence/relapse in rats self-administering heroin or cocaine. METHODS: Rats were trained to self-administer heroin (0.05 mg kg(-1) injection(-1)) or cocaine (0.5 mg kg(-1) injection(-1)) with each injection paired with a light cue. After stable responding was demonstrated, the floor near the levers was electrified, creating a barrier, in order to model the negative consequences of continued drug seeking. Shock intensities were increased over sessions until no responses occurred for three consecutive sessions. During a relapse test, where shock was maintained,the capacity of noncontingent drug cue presentations to induce active lever pressing was assessed. RESULTS: Ten of ten heroin animals and three of eight cocaine animals exposed to noncontingent cue presentations resumed responding. During the relapse test, for both drug groups, active lever pressing was significantly higher than during abstinence but only in the heroin group was it significantly higher than inactive lever pressing. CONCLUSIONS: The implementation of negative consequences for drug seeking can result in its cessation just as they might in human addicts. Similarly, exposure to drug cues can lead to resumption of drug seeking. This model may be useful for studying the mechanisms underlying abstinence and relapse and for developing strategies to prevent relapse.

The effects of strain and prenatal nicotine exposure on ethanol consumption by adolescent male and female rats.

Two studies of variables affecting voluntary ethanol consumption by adolescent male and female rats are reported. Sprague-Dawley (SD) and spontaneously hypertensive rats (SHRs) were compared in Experiment 1. Starting on postnatal day 30 all had 24-h access to 2%, then 4%, and then 6% ethanol, followed by 1-h access to the 6% until intake stabilized. During the 1-h access SHR females consumed more ethanol than all other groups. In Experiment 2, the same procedure was used to compare SD groups prenatally exposed to nicotine, with controls. Nicotine-exposed females consumed more ethanol during 1-h access than both nicotine-exposed and control males; but after using water intake as a covariate, the differences were not significant. These data show that deprivation conditions need to be considered when generalizing the results of voluntary consumption studies, and that estrogens may be a modulator of addictive behavior.