Academic journal article Canadian Journal of Experimental Psychology

Effects of Acute and Prolonged Opiate Abstinence on Extinction Behaviour in Rats

Academic journal article Canadian Journal of Experimental Psychology

Effects of Acute and Prolonged Opiate Abstinence on Extinction Behaviour in Rats

Article excerpt

Abstract We examined the role of withdrawal in relapse to drug-seeking and drug-taking by testing the effects of opiate abstinence on extinction behaviour in rats trained to self-administer heroin. Male Long-Evans rats responded for IV heroin under a heterogeneous chain (VI 120 s; FR 1) schedule in which "seeking" responses preceded a "taking" response which produced a drug infusion. Responding was then measured in extinction during acute (6, 12, and 24 hr) and prolonged (3, 6, 12, and 25 day) abstinence. Sucrose consumption and somatic withdrawal were assessed at each testing period. During acute abstinence, responses on the "drug-seeking" manipulandum increased at 24 hr, whereas responses on the "drug-taking" manipulandum increased at 6 hr. Both responses were elevated during the 12-day abstinence test. Sucrose consumption was reduced and somatic withdrawal scores were increased in opiate-experienced rats at each test period. Results suggest that heroin abstinence has different effects on drug-seeking and drug-taking and that these effects do not temporally coincide with somatic measures of opioid withdrawal.

Theories of drug addiction traditionally include drug abstinence as a critical feature of compulsive drug use. Different classes of drugs produce distinct withdrawal symptoms, but in all cases the aversive effects of drug abstinence are alleviated by the drug itself (Koob, Stinus, Le Moal, & Bloom, 1989). This suggests that drug abstinence may play a key role in maintaining drug self-administration, and may contribute to relapse after cessation of drug intake. Indeed, based on the premise that withdrawal acts as a negative reinforcer, many theories posit a major role for drug abstinence in the maintenance of, and relapse to, drug use (Gawin, 1989; Koob et al., 1989; Solomon & Corbit, 1974; Tiffany, 1990; Wilder, 1973). Nevertheless, there is surprisingly little evidence that drug abstinence plays a significant role in maintaining drug self-administration (Robinson & Berridge, 1993; Stewart & Vezina, 1988; Wise & Bozarth, 1987). For example, in both nonhuman and human subjects, there is no direct correlation between the severity of withdrawal symptoms and relapse tendencies following prolonged cocaine (Hughes, Higgins, & Bickel, 1994) or opiate (Shaham, Rajabi, & Stewart, 1996) use. Moreover, relapse to drug-taking in humans can occur even after overt signs of withdrawal have subsided (jaffe, 1990; Tiffany, 1990). To account for this latter phenomenon, it was suggested that conditioned cues associated with drug abstinence induce withdrawal and subsequent relapse following prolonged abstinence from morphine (Goldberg, Woods, & Schuster, 1969; Wilder & Pescor, 1970) or alcohol (Ludwig, Wilder, & Stark, 1974). Empirical evidence, however, does not appear to support this idea because the correlation between cue-- induced craving and withdrawal symptoms, at least in cocaine addicts, is weak (Childress, McLellan, Ehrman, & O'Brien, 1988), and self-reported craving for cocaine (Jaffe, Cascella, Kumor, & Sherer, 1989) and opiates (Ehrman, Ternes, O'Brien, & McLellan, 1992; Koob et al., 1989; Meyer & Mirin, 1979) is often highest immediately after drug administration, when withdrawal symptoms are alleviated.

Direct tests of the role of withdrawal in opiate selfadministration have also produced inconclusive findings. Rats trained under a "free-choice" drinking procedure for morphine increase their drug consumption during early withdrawal (Wikler & Pescor, 1970), but consumption levels remain elevated up to 72 days after the last morphine administration, even after overt somatic signs of withdrawal have ceased (Wilder & Pescor, 1967, 1970). Moreover, several studies reported that precipitating withdrawal in opiate-dependent animals by an injection of the opiate antagonist, naloxone, increases morphine self-administration (Goldberg, Woods, & Schuster, 1971; Goldberg et al. …

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