Antagonism of dermorphin-induced catalepsy with naloxone, TRH-analog CG3703 and the benzodiazepine antagonist, Ro 15-1788.

Intracerebroventricular (i.c.v.) administration of the highly selective opiate mu-receptor agonist, dermorphin, produced dose-dependent catalepsy in conscious rats. The cataleptic effect of dermorphin was abolished by pretreatment (intraperitoneal, i.p.) with the opiate-antagonist naloxone (5 mg/kg), thyrotropin-releasing hormone analog CG3703 (1 mg/kg) or the benzodiazepine-antagonist Ro 15-1788 (5 mg/kg) whereas pretreatment with the benzodiazepine alprazolam (1 mg/kg) potentiated the cataleptic effect of dermorphin. When given to cataleptic rats, naloxone and CG3703, but not Ro 15-1788, reversed the dermorphin-induced catalepsy. The data suggest an involvement of benzodiazepine receptors in the induction of catalepsy mediated by opioid mu-receptors. Other opioid-modulating neuronal systems, antagonized by CG3703, may be involved in maintaining the dermorphin-induced cataleptic state.