Electrophysiological effects of cyclazocine on rat cerebellar Purkinje neurons: comparison with phencyclidine.

Abstract

Cyclazocine is a benzomorphan which, in addition to more classical opiate properties, binds to the sigma opiate receptor site. Recently, it has been suggested that the sigma opiate receptor is identical to the binding site responsible for the actions of phencyclidine (PCP). Since the electrophysiological actions of PCP have already been demonstrated on rat cerebellar Purkinje neurons, the effects of cyclazocine were also studied in this system with the goal of comparing the electrophysiological effects of cyclazocine to those of PCP. Cyclazocine inhibited the spontaneous firing rates of Purkinje neurons. These responses were stereospecific and qualitatively appeared similar to the effects of PCP. Antipsychotic drugs, haloperidol and fluphenazine, partially antagonized the actions of cyclazocine, suggesting a catecholaminergic involvement similar to the mechanism proposed for PCP. Unlike PCP, the effects of cyclazocine were also partially reversed by the opiate antagonist, naloxone. Taken together, these results suggest that in the rat cerebellum cyclazocine may be interacting with at least two receptor mechanisms: a naloxone-sensitive opiate site, and a naloxone-insensitive site which might involve catecholaminergic mediation similar to the PCP mechanism of action. The naloxone-sensitive effects of cyclazocine, however, may be related to an interaction of the drug with kappa receptors rather than with the more classical mu or delta opiate mechanisms.