Effects of circadian disruption on methamphetamine consumption in methamphetamine-exposed rats.

RATIONALE: A substantial number of clinical studies indicate associations between sleep abnormalities and drug abuse; however, the role played by the circadian system in the development of addiction is largely unknown. OBJECTIVE: The aim of this study was to examine the effects of experimentally induced chronic jet lag on methamphetamine consumption in a rat model of methamphetamine drinking. METHODS: Male Sprague-Dawley rats (n = 32) were housed in running wheel cages in a 12:12 h light:dark cycle. One group of rats (n = 16) was given 2 weeks of forced methamphetamine consumption (0.01 % in drinking water; meth pre-exposed) while a second group (n = 16, not pre-exposed) received water only. This was followed by a 2-week abstinence period during which half of the animals from each group were exposed to four consecutive 6-h advancing phase shifts of the light:dark cycle, while the other half remained on the original light:dark cycle. Methamphetamine consumption was assessed in all rats following the deprivation period using a two-bottle choice paradigm. RESULTS: Methamphetamine consumption was initially lower in methamphetamine pre-exposed versus not pre-exposed rats. However, during the second week following abstinence, consumption was significantly higher in phase-shifted rats of the methamphetamine pre-exposed group compared to all other groups. CONCLUSIONS: These data reveal an effect of circadian rhythm disturbance on methamphetamine consumption and suggest that dysregulation of the circadian system be considered in the etiology of relapse and addiction.