The effect of benzodiazepines on the 5-HT agonist-induced head-twitch response in mice.
European journal of pharmacology – July 07, 1988
Source: PubMed
Summary
Benzodiazepines significantly enhance head-twitch responses in mice induced by certain serotonin receptor agonists, with clonazepam (10 mg/kg) notably increasing responses to 5-MeODMT without causing head-twitches on its own. In a study involving various agonists, none of the four tested benzodiazepines amplified responses from the indirect agonist 5-HTP, and some even inhibited them. This suggests that the potentiation occurs at postsynaptic sites rather than through traditional benzodiazepine receptors, indicating a complex interaction with serotonin pathways.
Abstract
The effects of four benzodiazepines (diazepam, clonazepam, oxazepam and clobazam) were studied on the head-twitch response induced in mice by several 5-HT receptor agonists. All the benzodiazepines tested potentiated the effects of the directly acting agonists 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine and mescaline, without themselves inducing head-twitches. In contrast, none of them potentiated head-twitches induced by the indirectly acting agonist 5-hydroxytryptophan (5-HTP; with carbidopa 25 mg/kg), and in some experiments a clear inhibition was seen. The clonazepam (10 mg/kg) potentiation of 5-MeODMT-induced head-twitches was not antagonised by flumazenil, (+)-bicuculline, or by pretreatment with p-chlorophenylalanine. Neither was it mimicked by muscimol, which inhibited head-twitches. These results indicate that the observed potentiation is not mediated by benzodiazepine receptors and that it occurs postsynaptically to the initiating 5-HT receptors. The inability of the benzodiapines to potentiate 5-HTP-induced head-twitches probably reflects a reduction in 5-HT neuronal activity mediated by benzodiazepine receptors, as co-administration of flumazenil and clonazepam potentiated the effects of 5-HTP whereas each compound alone had no effect.