Rotational behaviour produced in rats by unilateral electrolytic lesions of the ascending noradrenergic bundles

Abstract

Unilateral electrolytic lesions were made in the areas of the dorsal or the ventral noradrenergic bundles in rats to see if the motor and biochemical effects of unilateral electrolytic locus coeruleus lesions could be reproduced. Lesions of the locus coeruleus result in transient contraversive circling in response to systemically administered apomorphine and d-amphetamine, a transient rise in ipsilateral striatal dopamine and a permanent fall in ipsilateral cerebral cortical noradrenaline. Electrolytic lesions of the dorsal noradrenergic bundle area produced the opposite motor effect, with permanent ipsiversive circling in response to systemically administered apomorphine or d-amphetamine and a reduction in ipselateral cerebral cortical noradrenaline, but no increase in striatal dopamine. Control unilateral electrolytic lesions placed in the adjacent tectum sparing the dorsal bundle area produced neither rotational behaviour nor changes in brain noradrenaline or dopamine levels. Although the damaged area producing ipsiversive rotation included the dorsal noradrenergic bundle, it seems probable that damage to other structures caused this response. Electrolytic lesions of the dorsal bundle did not mimic the effects of electrolytic lesions of the locus coeruleus, and it is unlikely that this ascending pathway carries the fibres responsible for the circling behaviour and changes in striatal dopamine seen with locus coeruleus lesions. Unilateral electrolytic lesions restricted to the ventral noradrenergic bundle caused transient postoperative contraversive circling in response to apomorphine or d-amphetamine, and a transient elevation in the ipsilateral striatal dopamine content; these findings were present 5 days after operation and had disappeared by 1–3 months. Thus lesions of the ventral noradrenergic bundle alone reproduced the effects of lesions of the locus coeruleus. Extension of the lesion to involve the region of the dorsal noradrenergic bundle resulted in ipsiversive rotation in response to systemic apomorphine and d-amphetamine, even though the increase in ipsilateral striatal dopamine content still occurred. It is suggested that the similar findings produced by locus coeruleus and ventral bundle lesions are due to damage to noradrenergic fibres which pass from the locus coeruleus to the nigrostriatal system via the ventral bundle. This proposed pathway is envisaged as normally enhancing nerve impulse flow between the substantia nigra and the striatum. Alternatively, the circling produced by locus coeruleus lesions may be due to secondary alterations in raphe 5-hydroxytryptamine activity, which subsequently affects the nigrostriatal dopamine system.