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Effects of methamphetamine on development of circadian rhythms in rats
Insights
Continuous methamphetamine exposure in infant rats disrupts circadian rhythms of activity and corticosterone. These disruptions manifest as rhythm splitting and phase delays, impacting the developing circadian system.
Area of Science:
- Neuroscience
- Chronobiology
- Pharmacology
Background:
- The developing circadian system is sensitive to environmental influences.
- Methamphetamine is a stimulant with known effects on neurotransmitter systems involved in circadian regulation.
Purpose of the Study:
- To investigate the long-term effects of early-life methamphetamine exposure on the development of circadian rhythms in rats.
- To assess the impact on spontaneous locomotor activity and plasma corticosterone levels.
Main Methods:
- Infant rats received methamphetamine (0.005% in drinking water) from postnatal day 14.
- Locomotor activity and plasma corticosterone levels were monitored over several weeks.
- Circadian rhythm analysis, including entrainment and splitting, was performed.
Main Results:
- Locomotor activity rhythms initially showed normal development but later split into light-entrained and free-running components.
- Plasma corticosterone rhythms did not differ at 4 weeks but showed significant phase delay at 8 weeks.
- Rhythm splitting was not observed in the corticosterone data.
Conclusions:
- Continuous methamphetamine administration during development significantly alters circadian rhythms of locomotor activity and corticosterone in rats.
- These findings suggest methamphetamine disrupts the maturation and stability of the central circadian system.
- Potential mechanisms underlying these disruptions were discussed.
Abstract:
To determine the effect of continuous methamphetamine treatment on development of the circadian system, the daily courses of spontaneous locomotor activity and plasma corticosterone level were determined in infant rats. Methamphetamine was dissolved in drinking water at a concentration of 0.005%, and administered to rats from postnatal day 14. The circadian locomotor rhythm in methamphetamine treated rats was not significantly different from that in non-treated rats for the first 4 weeks of drug treatment. Then the rhythm began to show signs of relative coordination and finally split into two activity components. One component entrained to the light-dark cycle, whereas the other free-ran in spite of the light cycle. The rhythm of plasma corticosterone in the methamphetamine treated group was not different from that in the control group at 4 weeks after birth, but was significantly phase-delayed at 8 weeks. Splitting was not observed for the corticosterone rhythm. It is concluded that continuous administration of methamphetamine to infant rats affects the circadian rhythms for spontaneous locomotor activity and plasma corticosterone level. Possible mechanisms of methamphetamine effects were discussed in terms of the circadian system underlying these rhythms.