| Abstract No.: | B-E2170 |
| Country: | Canada |
| | |
| Title: | MODULATION OF SEROTONIN NEUROTRANSMISSION BY MELATONIN |
| | |
| Authors/Affiliations: | 4 Sergio Dominguez-Lopez*; 2 Ian Mahar; 1 Marco Leyton; 3 Gabriella Gobbi;
1 Deparment of Psychiatry, McGill University; 2 Department of Psychiatry, McGill University; 3 Department of Psychiatry, McGill University. Centre de Recherché Fernand Seguin, Université de Montréal ; 4 Deptarment of Psychiatry, McGill University, Montreal, QC, Canada
|
| | |
| Content: | Introduction: Melatonin (MLT) is a neuromodulator derived from serotonin (5-HT) synthesized mainly in the pineal gland following circadian and seasonal rhythms. MLT and 5-HT are both implicated in the pathogenesis of major depression and seasonal affective disorders, but their reciprocal relationship has not yet been characterized.
Objectives: In this study we explored 5-HT cell firing in the dorsal raphe nucleus (DR) after exogenous administration of MLT and endogenous suppression (pinealectomy) during the light phase of the circadian cycle.
Materials and Methods: Using in vivo single unit extracellular recordings in rats, we assessed 5-HT firing activity of DR neurons after i.v. injections of melatonin at different doses (1, 5, 20mg/kg of weight) as well as after endogenous suppression of melatonin secretion by pinealectomy (Px), comparing responses at different times of the light-dark cycle (morning, afternoon, evening).
Results: Across time of day, the administration of MLT (1mg/kg) significantly decreased 5-HT cell firing rates of 5-HT neurons for a period of 60 minutes following injection of 1mg/kg (CTRL: 0.88±0.06Hz; VEH: 0.85 ±0.19Hz; 1mg: 0.59 ±0.06Hz; 10mg: 0.77 ±0.09Hz; 20mg: 0.85 ±0.13, p<0.005). This reduction in the 5-HT cell firing rate produced by 1mg/kg was more significant particularly pronounced in the evening, as compared to morning-afternoon hours (16-20Hrs: 0.43 ±0.06Hz vs. 10-16Hrs: 0.72±0.09Hz, p<0.05); MLT decreased the firing rate as 75% of the neurons tested in the evening compared to only 35% of neurons tested in morning-afternoon. The effect pinealectomy was the opposite of MLT, and also was greatest in the evening, achieving statistical significance at this time-point only (16-20Hrs: CTRL: 0.82 ±0.17Hz; SHAM: 0.70 ±0.08Hz; Px: 1.36 ±0.14Hz, p<0.001; 10-16hrs CTRL: 0.82±0.09HZ; SHAM: 0.82±0.06HZ; Px: 0.73±0.07HZ, NS). Finally, neurons recorded in rats after Px during the evening hours also showed increased burst activity compared with rats after sham surgery (Px: 13.14±3.2 % of spikes in burst; SHAM: 4.84±2.14 % of spikes in burst, p<0.05).
Conclusion: These data suggest that melatonin exerts a fine-tuning modulation on the 5-HT system during the circadian rhythm; the 5-HT system seems to be more sensitive during the light to dark phase transition.
Acknowledgements: SDL is recipient of the CONACYT 193202/302017 Scholarship.
|
| | |
| Back |
|
