Actions and interactions of benzodiazepine agonists, antagonists and inverse agonists on suprahyoid muscle twitching

Amphetamine-induced twitching of the suprahyoid muscle in nialamide-pretreated, urethane-anaesthetised rats was inhibited by the benzodiazepine agonists RU 32007, diazepam and chlordiazepoxide and the GABAA agonist muscimol. Ro15-1788 and CGS 8216 induced slight, or no reduction in twitching, respectively, but reversed the effect of RU 32007 and diazepam. Ro15-1788 did not reverse the effect of muscimol. Picrotoxin reversed both muscimol and RU 32007 effects at a dose which induced only a small increase in twitching alone. Higher doses of picrotoxin markedly increased amphetamine twitching and induced twitching in the absence of amphetamine. Ethyl-beta-carboline-3-carboxylate (BCE) weakly increased twitching and reversed the effect of RU 32007. CL 218872 weakly reduced twitching but also weakly antagonised RU 32007. In rats pretreated with a higher dose of nialamide methyl beta-carboline-3-carboxylate (BCM) and BCE induced twitching. BCE-induced twitching was antagonised by RU 32007, Ro15-1788, CGS 8216, muscimol and weakly by CL 218872. Thus, benzodiazepine agonists inhibit twitching and inverse agonists induce twitching, both being blocked by antagonists. Partial agonism (CL 218872) or partial inverse agonism (CGS 8216) may be detected by differential effects against different inducers of twitching.