Pharmacological effects of melatonin treatment on both locomotor activity and brain serotonin release in rats

Abstract

The effects of intraperitoneal administration of pharmacological doses of melatonin (60 mg/kg) on both locomotor activity and brain monoamine release were assessed in rats. The spontaneous levels of either horizontal motion, vertical motion, or total distance traveled were decreased following melatonin injection. On the other hand, the spontaneous levels of postural freezing increased after treatment. External heat exposure (36 degrees C) produced increases in locomotion (including horizontal motion, vertical motion, and total distance traveled) as well as decreases of postural freezing in rats. The heat-induced increases of horizontal motion and total distance traveled as well as decreases of postural freezing were attenuated by melatonin treatment. In addition, cold exposure (4 degrees C) produced increases of vertical motion as well as decreases of postural freezing. Again, the cold-induced behavioral responses were attenuated by melatonin treatment. Biochemical data revealed that the serum levels of melatonin were decreased by both heat and cold exposure in rats. Furthermore, voltammetric data revealed that intraperitoneal administration of melatonin (60 mg/kg) decreased serotonin, but not the dopamine, release in the hypothalamus, the corpus striatum or nucleus accumbens of rat brain. Neither the locomotor activity responses to thermal stress nor brain monoamine release was affected by a smaller dose of melatonin (30 mg/kg, i.p.). The results suggest that systemic administration of melatonin, at pharmacological doses, inhibits brain serotonin release and results in a reduction in both the spontaneous locomotion and the thermal stress-induced locomotor activity responses in rats.

Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade

“…In contrast to BZPs, 5-HT 2C receptor antagonists do not modulate 5-HT release in corticolimbic structures (Gobert et al 2000;Millan et al 2000b) and, accordingly, SB243,213 failed to modify extracellular levels of 5-HT in FCX or dorsal hippocampus. Though it has been proposed that high doses of melatonin modulate cerebral 5-HT release under certain conditions, data remain fragmentary (Chuang and Lin 1994;Yoshioka et al 2000) and no effect of melatonin on extracellular levels of 5-HT was observed herein. In line with this lack of influence of SB243,213 and melatonin on 5-HT levels, they were not affected by agomelatine.…”

Antidepressant-like effects of agomelatine, melatonin and the NK1 receptor antagonist GR205171 in impulsive-related behaviour in rats

“…30 mg kg −1 , p.o.) of melatonin may modulate (enhance or reduce) 5-HT release within some cerebral structures (Chuang and Lin 1994;Yoshioka et al 2000), whereas other studies, also with high doses, led to the conclusion that melatonin does not affect 5-HT release in main projection areas of 5-HT neurones such as frontal cortex and hippocampus (Millan et al 2005). Using considerably lower doses, ex vivo studies indicated that melatonin (0.5 or 1 mg kg −1 , s.c.) increased tissue levels of 5-HT and 5-HIAA in most hypothalamic structures, in the amygdala and in the midbrain, but displayed an inhibitory effect on 5-HT turnover in suprachiasmatic nuclei (Miguez et al 1994(Miguez et al , 1996.…”

Domoic acid-induced neurotoxicity in the hippocampus of adult rats

“…Melatonin has anticonvulsant and depressive effects (Acuna-Castroviejo et al, 1995) and anti-excitotoxic efficacy in reduction of induced locomotor responses (Chuang and Lin, 1994). Melatonin has a potent protective effect against neurological injuries produced by agents or processes such as aging (Reiter et al, 2001;Sharman et al, 2002), stroke , trauma (Mesenge et al, 1998;Pei et al, 2002), ischemia (Sun et al, 2002), and excitotoxins like KA and quinolinic acid (Melchiorri et al, 1995;Giusti et al, 1996;Tan et al, 1998;Chung et al, 2003).…”