High concentrations of diazepam-binding inhibitor (DBI) have been detected in brain areas containing dopaminergic cell bodies and nerve terminals. In the present study, we have investigated the effect of a proteolytic fragment of DBI, the octadecaneuropeptide ODN, on apomorphine-induced yawning in Sprague-Dawley rats. Injection of graded doses of ODN (12.5 to 100 ng i.c.v.) caused a dose-dependent inhibition of apomorphine-induced yawning and penile erections. At a dose of 100 ng, intracerebroventricularly administered ODN was able to inhibit, during more than 3 h, the apomorphine-evoked yawning. ODN also inhibited pilocarpine-induced yawning. Apomorphine induces a bell-shaped dose-dependent effect on yawning with a maximum response at the dose of 100 microg/kg and a much lower effect at a dose of 200 microg/kg. Injection (i.c.v.) of 100 ng ODN markedly attenuated the number of yawns induced by 100 microg/kg apomorphine but partially restored the yawning behavior in rats treated with a 200 microg/kg dose of apomorphine. At doses of 0.5 or 5 mg/kg s.c., diazepam did not modify the inhibitory effect of ODN on the apomorphine-induced yawning. Taken together, the present data suggest that ODN inhibits yawning downstream dopaminergic as well as cholinergic synapses involved in yawning. In addition, the effect of ODN cannot be ascribed to an inverse agonistic activity on central-type benzodiazepine receptors.