EFFECT OF NALTREXONE AND ITS DERIVATIVES, NALMEFENE AND NALTRINDOLE, ON CONDITIONED ANTICIPATORY BEHAVIOR AND SACCHARIN INTAKE IN RATS

Drug craving, the desire to re-experience the effects of a psychoactiv e substance, may be an important influence on drug-seeking and drug-ta king behaviour. In rats, drug-seeking behaviour can be operationalized as conditioned anticipatory behaviour, evidenced by frequent visits t o, and an increased time spent and distance travelled in, the drug adm inistration area prior to the availability of the reinforcer. The effe cts of the opioid antagonist, naltrexone, and its derivatives, nalmefe ne and naltrindole, on conditioned anticipatory behaviour and drinking -associated behaviour and fluid intake during the access phase were ex amined. Male Wistar rats were trained to consume 0.1% saccharin and wa ter in a distinct environment in a free-choice limited-access procedur e. Naltrexone (0.3, 1 mg/kg) decreased conditioned anticipatory behavi our and drinking-associated behaviour in the saccharin zone without af fecting the corresponding behaviour in the water zone. Its derivatives had different effects. Nalmefene (0.1 mg/kg) increased drinking-assoc iated behaviour but not conditioned anticipatory behaviour, whereas na ltrindole (1, 2 mg/kg) modestly decreased conditioned anticipatory beh aviour but not drinking-associated behaviour. Naltrexone (0.3, 1 mg/kg ) and naltrindole (1, 2 mg/kg), but not nalmefene, selectively decreas ed saccharin intake. These findings suggest that the blockade of selec tive opioid receptors may differentially alter conditioned anticipator y behaviour, drinking-associated behaviour and consumption levels, and that these behaviours can be modified separately.