Neuropeptide modulation of the behavioral effects of drugs.

Studies employing conditioned operant behavior of squirrel monkeys, rabbits and pigeons have demonstrated that the neuroactive peptides thyrotropin-releasing hormone (TRH), substance P (SP) and neurotensin (NT) produce marked behavioral effects under a wide range of procedures. These compounds appear to be particularly active when given in combination with other drugs. The co-administration of TRH with chlordiazepoxide, pentobarbital and ethanol potentiates the effects of these agents on punished behavior. Under other conditions SP can reverse the effects of chlordiazepoxide, whereas NT enhances the effects of haloperidol. Neither TRH, SP nor NT are behaviorally active at doses that produced significant interactions. These results support the view that neuropeptides exert modulatory effects on various neurotransmitter systems. An understanding of peptide-drug interactions should contribute to the development of new compounds with enhanced psychopharmacological efficacy and minimal side effects.