The roles of noradrenaline and dopamine in contraversive circling behaviour seen after unilateral electrolytic lesions of the locus coeruleus

Abstract

Unilateral electrolytic lesions of the locus coeruleus in rats result in spontaneous ipsiversive rotation, which is then replaced by contraversive rotation. One week after lesioning, when spontaneous turning ceases, apomorphine and d-amphetamine elicit contraversive circling behaviour, which was not affected by noradrenergic receptor blockade but was abolished by dopamine receptor blockade. The drug-induced contraversive circling response was also reproduced by piribedil but not clonidine. Combined unilateral electrolytic locus coeruleus and substantia nigra lesions on the same side resulted in apomorphine- and d-amphetamine-induced ipsilateral rotational behaviour which was indistinguishable from that seen with substantia nigra lesions alone. In rats with unilateral locus coeruleus lesions, the dose of intrastriatally injected apomorphine required to produce circling was less on the lesioned than the non-lesioned side. Direct injection of noradrenaline into one substantia nigra caused contraversive circling. Direct injection of phenoxybenzamine into one substantia nigra followed by apomorphine caused ipsiversive circling. The results suggest that the circling behaviour seen after unilateral locus coeruleus lesions depends on an asymmetry of striatal dopamine receptor activity and are consistent with a proposed coeruleus-nigral noradrenergic pathway, which enhances impulse flow in the dopaminergic nigrostriatal system.