Chronic food restriction in rats augments the central rewarding effect of cocaine and the delta(1) opioid agonist, DPDPE, but not the delta(2) agonist, deltorphin-II

Rationale: Chronic food restriction augments the self-administration and lo comotor stimulating effects of opiates, psychostimulants and NMDA antagonis ts. The extent to which these effects can be attributed to changes in drug pharmacokinetics and bioavailability versus sensitivity of the neuronal cir cuits that mediate the affected behavioral functions, has not been establis hed. Recent studies point to central adaptive changes insofar as rewarding, locomotor and c-fos-inducing effects of amphetamine and MK-801, injected d irectly into the lateral ventricle, are greater in food-restricted than ad libitum fed rats. The increased expression of c-fos in nucleus accumbens (N AC) shell, in particular, suggests that food restriction may augment drug r eward by modulating dopamine (DA) synaptic function in this area. Objective s: The first purpose of this study was to investigate whether the rewarding effects of cocaine and the delta (1) opioid agonist DPDPE, both of which i ncrease DA synaptic transmission, are augmented by food restriction. The se cond purpose was to determine whether the delta (2) opioid agonist, deltorp hin-II, which has been reported to exert DA-independent rewarding effects, is subject to the potentiating effect of food restriction. Methods: Rewardi ng effects of drugs were measured in terms of their ability to lower the th reshold for lateral hypothalamic self-stimulation (LHSS) using a rate-frequ ency method. Results: In separate experiments, cocaine (50, 100 and 150 mug , ICV) and DPDPE (10 and 25 mug, ICV) produced greater threshold-lowering e ffects in food-restricted than ad libitum fed rats. Deltorphin-II (5.0, 10 and 25 mug, ICV) had no effect on reward thresholds, regardless of feeding regimen. Conclusions: While the reported DA-independence of deltorphin-II r ewarding effects seemed to offer a means of testing the hypothesis that DA transmission is the critical modulated variable in food-restricted subjects , rewarding effects of this compound could not be demonstrated in the LHSS paradigm. The present results do, however, confirm and extend prior finding s indicating that the enhanced self-administration of abused drugs by food- restricted subjects is due to enhanced sensitivity of a final common pathwa y for drug reward.