Effects of age on serotonergic and noradrenergic of GABAergic neuronal interaction

中枢神経系に対する加齢効果の行動薬理学的研究

Effects of age on serotonergic and noradrenergic of GABAergic neuronal interaction

Creators Soeda Koichiro

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.

[ISSN]0513-1731

[NCID]AN00243156