The effects of the GABA-mimetic drugs, progabide and baclofen, on the biochemistry and function of 5-hydroxytryptamine and noradrenaline.

Administration to mice of a single dose of (+/-)-baclofen (5 mg/kg) or progabide (100 mg/kg) significantly inhibited the head-twitch response mediated by 5-hydroxytryptamine (5-HT2) receptors 30 min (but not 3 hr) later, when the response was produced by injection of carbidopa (25 mg/kg) plus 5-hydroxytryptophan (5-HTP; 100 mg/kg). No change was seen in the head-twitch response when induced at this time by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT; 5 mg/kg). Inhibition of the head-twitch response after injection of 5-HTP was produced by pretreatment with (-)-baclofen, but not (+)-baclofen; injection of (+)-baclofen with the (-)-baclofen did not alter the attenuation of the behaviour produced by the active isomer. Twenty-four hours after the last injection of progabide, given repeatedly (100 mg/kg injected 5 times over 10 days) specific binding of [3H]ketanserin in the frontal cortex was enhanced and the head-twitch response to both 5-HTP and 5-MeODMT was markedly increased. The sedation response mediated by alpha 2-adrenoceptors, which followed the injection of clonidine (0.25 mg/kg) was attenuated. Repeated administration of baclofen (10 mg/kg per day in drinking water) also increased the number of 5-HT2 receptors in the frontal cortex (16%) and enhanced the head-twitch behaviour after injection 5-HTP or 5-MeODMT. Clonidine-induced sedation, number of beta-adrenoceptors in the cortex and apomorphine-induced locomotor activity were all unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)