Effects of chronic clonidine administration and withdrawal on free-running circadian activity rhythms

This study examined the effects of the alpha 2-adrenergic agonist clonidine on free-running circadian activity rhythms in rats, using a dosing regimen similar to one previously shown to induce behavioral depression in the swim test. In constant light, clonidine consistently shortened the free-running circadian period, reduced circadian amplitude, and reduced the overall level of locomotor activity. These effects were reversed after the termination of clonidine treatment. In constant darkness, clonidine reduced circadian amplitude, but both increases and decreases in free-running period and activity level were observed. Clonidine-induced changes in free-running period and activity level were systematically related to individual differences in baseline activity in both constant light and constant darkness. These results demonstrate that clonidine can alter both the rhythmicity and the level of spontaneous activity, and are consistent with the hypothesis that monoaminergic systems may mediate relationships between behavioral state and circadian rhythmicity.