Related Experiment Videos
Neonatal clomipramine treatment, alcohol intake and circadian rhythms in rats
1Department of Psychology, University of Maine, Orono 04469, USA.
Insights
Neonatal exposure to clomipramine, an antidepressant, altered circadian rhythms and increased alcohol intake in rats. These findings suggest changes in rhythm amplitude and coherence are key in animal models of depression.
Area of Science:
- Neuroscience
- Chronobiology
- Pharmacology
Background:
- Neonatal exposure to monoamine re-uptake inhibitors can induce depression-like behaviors in adult rats.
- Depression is associated with altered circadian rhythmicity in humans.
- Previous studies showed neonatal desipramine altered circadian rhythms and increased alcohol intake in male rats.
Purpose of the Study:
- To investigate the effects of neonatal clomipramine treatment on circadian drinking rhythms and alcohol intake in male and female rats.
- To examine the impact of alcohol exposure on circadian rhythmicity in these rats.
Main Methods:
- Neonatal rats received clomipramine (25 or 30 mg/kg) or saline on postnatal days 8-21.
- Free-running circadian drinking rhythms were assessed in constant darkness and constant light.
- Voluntary alcohol (10% ethanol) intake was measured.
- Circadian parameters including period, amplitude, and spectral magnitude were analyzed.
Main Results:
- Neonatal clomipramine did not alter the free-running period of circadian drinking rhythms.
- Clomipramine treatment increased spectral magnitude in both sexes and circadian amplitude in females.
- Neonatal clomipramine exposure increased voluntary alcohol intake.
- Alcohol consumption shortened the circadian period in both clomipramine- and saline-treated groups.
Conclusions:
- Alterations in circadian rhythm amplitude and spectral magnitude, rather than period, may be more indicative of depression-like states in animal models.
- Neonatal clomipramine exposure impacts circadian rhythmicity and increases alcohol consumption, offering insights into antidepressant effects and depression pathophysiology.
Abstract:
Neonatal exposure to antidepressant monoamine re-uptake inhibitors produces a wide variety of effects on the behavior and physiology of adult rats which are consistent with features of clinical depression. Since depressed patients show characteristic alterations in circadian rhythmicity, our laboratory has examined free-running circadian drinking rhythms in this putative animal depression model. Previously, neonatal desipramine treatment was shown to lengthen free-running period, and increase circadian amplitude, spectral magnitude, and voluntary alcohol intake (10% ethanol v/v) of male rats. The purpose of the present study was to examine the effects of neonatal clomipramine treatment (25 or 30 mg/kg s.c., postnatal days 8-21) on circadian drinking rhythms and alcohol intake of both male and female rats. In addition, effects of alcohol exposure on circadian rhythmicity were also examined. Contrary to expectations, free-running period of clomipramine-treated rats did not differ from saline-treated controls in either constant darkness (DD) or constant light (LL), but spectral magnitude was increased in clomipramine-treated males and females, and circadian amplitude was increased in clomipramine-treated females. Neonatal clomipramine also increased voluntary alcohol intake, and both clomipramine- and saline-treated groups displayed significant period-shortening during alcohol exposure. Taken together, these results suggest that alterations in the amplitude and coherence of circadian rhythmicity may be more consistent than alterations in free-running period in animal depression models, as has been suggested previously for depressed patients.