Chronic BMY7378 treatment alters behavioral circadian rhythms
Jhenkruthi Vijaya Shankara1,2, Angélique Orr1, Richelle Mychasiuk1,2,3
1Department of Psychology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada.
The European Journal of Neuroscience
|October 19, 2017
Summary
Chronic BMY7378 treatment alters hamster circadian rhythms and serotonin receptor expression. This highlights adaptive brain changes to long-term serotonergic drug use, impacting circadian parameters.
Area of Science:
- Chronobiology
- Neuropharmacology
- Circadian Rhythms
Background:
- The mammalian circadian clock synchronizes to the light:dark cycle.
- Serotonin modulates light's effect on circadian rhythms.
- Mixed 5-HT1A agonist/antagonists acutely potentiate light-induced phase advances.
Purpose of the Study:
- To investigate the chronic effects of the mixed 5-HT1A agonist/antagonist BMY7378 on circadian parameters in hamsters.
- To examine adaptive changes in serotonin receptor mRNA expression following chronic BMY7378 administration.
Main Methods:
- Adult male hamsters received chronic (28-day) administration of BMY7378 or vehicle via osmotic mini pumps.
- Circadian rhythms were assessed under light:dark cycles and constant darkness.
- Quantitative real-time PCR (qRT-PCR) analyzed mRNA levels of serotonin receptors and related enzymes in brain regions.
Main Results:
- Chronic BMY7378 advanced the phase angle of entrainment, prolonged the active phase, and attenuated rhythm amplitude in a light:dark cycle.
- BMY7378 attenuated light-induced phase advances but not delays in constant darkness.
- Non-photic phase shifts were also attenuated by chronic BMY7378.
- Upregulation of 5-HT1A and 5-HT1B mRNA in the hypothalamus and downregulation of 5-HT1A and monoamine oxidase-A mRNA in the brainstem were observed.
Conclusions:
- Chronic BMY7378 induces adaptive changes in brain serotonin receptor expression.
- These neurochemical adaptations correlate with significant alterations in circadian rhythm parameters.
- Long-term effects on the circadian system should be considered for patients on chronic serotonergic medications.
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