Stereoselective effects of opiate agonists and antagonists on ingestive behavior in rats

In male Sprague Dawley rats, the (-)-isomer of the opiate antagonist GPA 1843 (beta-9-methyl-5-phenyl-2-allyl-2'-hydroxy-6, 7-benzomorphan) produced dose-related decreases in nocturnal feeding and of hyperphagias induced by 2-deoxy-D-glucose (2-DG; 400 mg/kg) and 24 hr food deprivation (FD). The hyperphagia induced by insulin (10 U/kg) was not significantly decreased by GPA 1843. In contrast, comparable doses of the (+)-stereoisomer, GPA 1847, had no effect on nocturnal, 2-DG or FD hyperphagia. In addition, hyperphagia and hyperdipsia were observed following administration of the opiate agonist levorphanol, but not its stereoisomer, dextrorphan. Thus, the effects of these agents on consummatory behavior are mediated by a stereospecific interaction with opiate receptors, which further indicates that endogenous opiate peptides are involved in the expression of these opiate-related hyperphagias.