Locomotor activity of rats after stimulation of the nucleus locus coeruleus region or after lesion of the dorsal noradrenergic bundle: effects of clonidine, prazosin and yohimbine.

Abstract

We previously showed in the rat that electrical stimulation of the nucleus locus coeruleus produced, 4 weeks later, a significant increase in the number of α1 and α1 in the cerebral cortex. In a parallel pharmacological study, we tested the effects of small doses of clonidine on the locomotor activity of stimulated rats and implanted but not stimulated animals. In stimulated rats only, clonidine had a dual effect: firstly, sedation 30 min after injection, and secondly, hyperactivity which was observed 24 h after injection. In the present study, using the same behavioral paradigm, we tested the effects of small doses of clonidine on the locomotor activity of three groups of rats: stimulated in the locus coeruleus, lesioned in the dorsal noradrenergic bundle and controls. In stimulated rats injected with clonidine, delayed hyperactivity appeared 24 h after the injection, beginning at the smallest dose used (2.5 μg/kg). This hyperactivity was not due to the stimulation per se, since it did not appear in stimulated rats injected with the vehicle. In rats with dorsal noradrenergic bundle lesions, this delayed hyperactivity was observed only after a high dose (50 μg/kg) of clonidine. In a second experiment, we tested the effect of small doses of prazosin or of yohimbine on the delayed, drug-induced, hyperactivity of stimulated or lesioned rats. In stimulated rats, prazosin (an α1-adrenoceptor antagonist) suppressed the hyperactivity produced by clonidine. Yohimbine (an α2-adrenoceptor antagonist) markedly increased the locomotor activity of stimulated rats injected with vehicle. Likewise, in lesioned rats, prazosin suppressed the hyperactivity produced by a dose of 50 μg/kg of clonidine. These results are interpreted in relation to the possible role of α-adrenoceptors in the regulation of locomotor activity.