A SEROTONIN NEUROTOXIN ATTENUATES THE PHASE-SHIFTING EFFECTS OF TRIAZOLAM ON THE CIRCADIAN CLOCK IN HAMSTERS

Several lines of evidence suggest the potential involvement of seroton ergic pathways in mediating the effects of activity-inducing stimuli o n the circadian clock in rodents. The aim of the present 3 experiments was to examine the effects of the serotonergic neurotoxin, p-chloroam phetamine (PCA, 10 mg/kg) on: (1) the monoamine levels of the hypothal amus, frontal cortex and hippocampus in the hamster; (2) the phase shi fts in the circadian rhythm of locomotor activity of hamsters in respo nse to treatment with the short-acting benzodiazepine, triazolam (7.5 mg/kg); and (3) the magnitude of the acute increase in locomotor activ ity associated with triazolam administration in this species. The admi nistration of PCA to hamsters caused changes of specific monoaminergic systems in the hypothalamus, that were limited to a selective decreas e in serotonin levels 7 days post-treatment. The phase shifts of the c ircadian clock in response to triazolam treatment at CT 6 were conside rably attenuated following the administration of the 5-HT neurotoxin. The total amount and the profiles of triazolam-induced wheel-running a nd general cage activity between CT 6 and CT 12 were not significantly affected by the PCA treatment. The finding that a 5-HT neurotoxin can attenuate the phase-shifting effects of triazolam in hamsters, withou t interfering with its activity-inducing properties, suggests that ser otonergic afferents might be involved in the mechanism for non-photic phase-shifting of the circadian system.