Effects of age on serotonergic and noradrenergic of GABAergic neuronal interaction

This study was performed in an attempt to clarify the effect of age (mice aged 2 and 10 months) on serotonetgic and noradrenergic or GABAergic neuronal interaction involved in head twitches induced by 5-methoxy-N, N-dimetyltryptamine, a direct serotonin adonist, and fenfluramine, a serotonin releaser. Intraperitoneal injection of 5-MeODMT and fefluramine produced ad higher frequency of head twitches in 10-month-old mice than in 2-month-old mice. Pretreatment with clonideine, an alpha-2 receptor agonist, significantly inhibited 5-MeODMT- and fenfluramine-induced head twitches in both 2- and 10-month-old mice. Tohimbine, an alpha-2 receptor antagonist, significantly potentiated both 5-MeODMT- and fenfluramine-induced head twicthes in 2-month-old mice but did not affect both them in 10-month-old mice. In 2-month-old mice, pretreatment with aminooxyacetic acid (AOAA), a GABA transferase inhibitor, significantly potentiated 5-MeODMT-induced head twitches, and tended to increase fenfluramine-induced head twitches but not significantly. In 10-month-old mice, oretreatment with AOAA significantly inhibited both 5-MeODMT- and fenfluramine-induced head twitches. Pretreatment with baclofen, a GABA_b agoist, significantly inhibited both 5-meODMT- and fenfluramine-induced head twitches in 2- and 10-month-old mice. These results suggest that 1) 10-month-old mice produce hypersensitivity of post-synaptic serotonergic receptor, 2) sensitivity of alpha-2 adrenoceptors which regulate serotonergic neurons may be decreased in 10-month-old mice, but there is a possibility that alpha-2 adrenoceptors are still activated by alpha-2 adrenoceptor stimulant, 3) sensitivity of GAGA_a receptors which regulate serotonergic neurons is relatively higher than those of GABA_b receptors in 2-month-old mice, and in 10-month-old mice, GABA_b receptor activities are more dominant, and 4) there is a possibility that hyperactivity of serotonergic neurons is independent from GABA receptor activities (especially GABA_b), but may, at least in part, involve hyposensitivity of alpha-2 aderenoceptors.