Antagonism of the effects of the atypical benzodiazepine, Ro 5-4864 on intracranial self-stimulation in the rat.

The effects of Ro 5-4864 (chlordiazepam) were examined on responding for self-stimulation of the mid-lateral hypothalamus. Rewarding stimuli were delivered according to a 10-sec variable interval schedule of reinforcement. Ro 5-4864 (10-30 mg/kg, subconsulsive doses in these rats) decreased responding. This effect was antagonized by chlordiazepoxide (5-10 mg/kg) and phenobarbitone (35 mg/kg) but not by the benzodiazepine receptor antagonist Ro 15-1788 (10-20 mg/kg), the ligand for peripheral benzodiazepine receptors PK 11195 (60 mg/kg) or phenytoin (60 mg/kg). The pattern of interactions of Ro 5-4864 with these compounds differs from the pattern obtained with other procedures, and suggests that Ro 5-4864 has effects on systems unrelated to anxiety, convulsive activity or sedation.