Effects of carbamazepine on 5-hydroxytryptamine function in rodents

Abstract

The effects of carbamazepine (CBZ) on brain 5-hydroxytryptamine (5-HT) function were investigated in rodents pretreated with CBZ acutely or for 14 days. In behavioural experiments, mice pretreated with 14 days CBZ showed increased 5-HT₂-mediated head twitch behaviour after injection of carbidopa (25 mg/kg) followed by 5-hydroxytryptophan (5-HTP, 100 mg/kg). However, no change in head twitches after 5-methoxy,N,N,-dimethyltryptamine (5MeODMT 5.0 mg/kg), a direct agonist, was observed. Chronic CBZ administration to rats did not alter either the behavioural syndrome induced by 8-hydroxy-2-dipropy-laminotetralin (8-OH-DPAT, 1.0 mg/kg), an index of post-synaptic 5-HT_1A responses, or hypothermia after 8-OH-DPAT (0.5 mg/kg) which is thought to reflect presynaptic 5-HT_1A activity. Both hyperactivity and the behavioural syndrome seen after tranylcypromine (20 mg/kg) followed byl-tryptophan (100 mg/kg) were decreased by prior treatment with CBZ (14 days). Accumulation of 5-HTP after administration of the amino acid decarboxylase inhibitor NSD1015 (100 mg/kg) was decreased after acute CBZ (50 mg/kg) in hippocampus. However, after 14 days oral treatment no change in this measure of 5-HT synthesis was seen, in either hippocampus or frontal cortex. CBZ (50 µM) added to superfused brain slices did not affect potassium-stimulated [³H]-5-HT release. However, hippocampal slices from rats pretreated with CBZ (14 days) showed increased potassium-stimulated [³H]-5-HT release. CBZ (14 days) did not alter 5-HT₂ binding in rat frontal cortex. These results indicate a depressant effect of acute CBZ upon presynaptic 5-HT activity and an increase in presynaptic 5-HT function when CBZ is given for 14 days. Post-synaptic 5-HT function was, however, not altered by CBZ.