Abstract
Melatonin is synthesized by the pineal gland with a circadian rhythm in synchrony with the environmental light/dark cycle. A gradual increase in circulating levels of melatonin occur after lights off, reaching its maximum around the middle of the dark phase. Agonists of melatonin receptors have proved effectiveness as antidepressants in clinical trials. However, there is contradictory evidence about the potential antidepressant effect of melatonin itself. Herein we studied melatonin administration in mice at two zeitgeber times (ZT; ZT = 0 lights on; 12:12 L/D), one hour before the beginning (ZT11) and at the middle (ZT18) of the dark phase after either a single or a three-dose protocol. Behavioral despair was assessed through a forced-swimming test (FST) or a tail suspension test (TST), at ZT18.5. A single dose of 4 mg/kg melatonin at ZT11 was effective to reduce the immobility time in both tests. However, acute administration of melatonin at ZT18 was not effective in mice subjected to FST, and a higher dose (16 mg/kg) was required to reduce immobility time in the TST. A three-dose administration protocol of 16 mg/kg melatonin (ZT18, ZT11, and ZT18) significantly reduced immobility time in FST. Data indicate that the timely administration of melatonin could improve its antidepressant-like effect.
Highlights
In vertebrates, melatonin (N-acetyl-5-methoxytryptamine) is synthesized by the pineal gland during the dark phase of the light/dark cycle
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We demonstrated that melatonin administered one hour before lights off (ZT11) decreased immobility in Swiss Webster mice when tested in the forced-swimming test (FST) and in the TST, with this effect being more pronounced in the later test
Summary
Melatonin (N-acetyl-5-methoxytryptamine) is synthesized by the pineal gland during the dark phase of the light/dark cycle. This gland receives a neuronal noradrenergic input from an efferent pathway originating in the suprachiasmatic nucleus. In response to this signal, pinealocytes synthesize melatonin [1]. Current evidence indicates that melatonin synthesized in extrapineal sites does not contribute to the plasma circulating melatonin and is not related to the environmental photoperiod (for a review see Acuña-Castroviejo et al, 2014) [9]
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