Free-running circadian activity rhythms during long-term clonidine administration in rats

Experimental and clinical studies indicate that the alpha-adrenergic agonist clonidine can alter mood and activity. However, the behavioral effects of this agent are complex and appear to depend on duration of treatment. Recent work from this laboratory demonstrated that clonidine systematically alters the period, amplitude, and level of free-running circadian activity rhythms in rats. The present study confirms and extends previous observations by employing a longer duration of clonidine treatment. The results show that chronic clonidine administration reversibly shortens the free-running period and reduces the amplitude of the free-running rhythm in constant light. Furthermore, clonidine treatment can increase or decrease the level of activity, depending on baseline activity level, and these effects are not consistently reversed following the termination of treatment. These observations support the hypothesis that noradrenergic systems influence both the circadian periodicity and the level of spontaneous activity, and that clonidine may influence these two parameters by acting at different neural or neuronal loci.