Separation of clonazepam-induced head twitches and muscle relaxation in mice

Stereotyped head twitches in mice were induced by clonazepam. The number of head twitches produced was directly related to the clonazepam dose. In addition to head twitches, clonazepam produced dose-related muscle relaxation. Methysergide antagonized the action of clonazepam on head twitches. However, methysergide failed to block the muscle relaxant action. In contrast to methysergide, the benzodiazepine receptor antagonists CGS 8216 and Ro 15-1788 blocked the muscle relaxant effects of clonazepam. Neither CGS 8216 nor Ro 15-1788 blocked the clonazepam-induced head twitches. These data suggest that the muscle relaxant effects of clonazepam are mediated by benzodiazepine/GABA receptor systems that can be blocked by CGS 8216 and Ro 15-1788. On the other hand, it is proposed that the benzodiazepine-induced head twitch effect is mediated by a benzodiazepine/serotonin 2 receptor system.