The effect of benzodiazepines on the 5-HT agonist-induced head-twitch response in mice.
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.
Moser
P C
PC
School of Pharmacy and Pharmacology, University of Bath, U.K.
Redfern
P H
PH
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001569:Benzodiazepines / Q000494:pharmacology*; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D051379:Mice; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D008732:Methoxydimethyltryptamines; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D001569:Benzodiazepines; D012701:Serotonin; D006916:5-Hydroxytryptophan