ACAMPROSATE SUPPRESSES THE EXPRESSION OF MORPHINE-INDUCED SENSITIZATION IN RATS BUT DOES NOT AFFECT HEROIN SELF-ADMINISTRATION OR RELAPSE INDUCED BY HEROIN OR STRESS

Acamprosate (calcium-acetyl homotaurinate) is a new compound used in t he treatment of alcohol abuse, Because of the putative link between al coholism and the endogenous opioid systems in both humans and laborato ry animals, we tested in rats the effects of acamprosate on behavioral and neurochemical effects of opioid drugs related to their abuse pote ntial. These included sensitization to the behavioral effects of morph ine, morphine-induced dopamine (DA) release in the nucleus accumbens ( NAS), intravenous (IV) heroin self-administration and relapse to heroi n seeking in drug-free rats. In experiment 1, rats were injected daily with either morphine (10 mg/kg, SC) or saline for 14 days. Three days later in a test for the expression of sensitization, an injection of morphine (10 mg/kg) resulted in increased locomotor activity and enhan ced DA release in the NAS in rats previously exposed to morphine. Acam prosate (two injections of 200 mg/kg; 12 h apart; IP) suppressed the e xpression of the sensitized responses, but did not alter the effects o f morphine in drug-naive control rats, In experiment 2, it was found t hat acamprosate (two injections of 50-200 mg/ kg; IP) had no consisten t effects on IV heroin self-administration (50-100 mu g/kg per infusio n) and, in experiment 3, that acamprosate (100-200 mg. kg, IP) did not alter reinstatement of drug seeking induced by priming injections of heroin (0.25 mg/kg, SC) or a footshock stressor (15 min; 0.5 mA) after a 5- to 8-day period of extinction. Thus, although acamprosate attenu ated the expression of sensitized locomotor activity and DA release in the NAS, it did not have any consistent effect on either the intake o f heroin during the maintenance phase or the relapse to heroin seeking in a drug-free state. Thus, to the extent that the self-administratio n and the reinstatement procedures provide valid preclinical models fo r drug use and relapse in humans, our data suggest that acamprosate ma y not be effective in altering drug-taking behavior in heroin users.