Does contralateral circling involve action of drugs on hyposensitive striatal dopamine receptors in the hemisphere contralateral to denervation?

Abstract

Rats receiving unilateral intrastriatal injections of 6-hydroxydopamine (6-OHDA) (3 × 16μg. in the presence of tranylcypromine and desmethylimipramine (DMI), resulting in 84% dopamine depletion) exhibited contralateral asymmetry and circling behaviour on peripheral challenge with apomorphine or on unilateral intrastriatal injection of dopamine (into the denervated striatum) (resulting in a stable response after 8 days). The denervated striatum was markedly more sensitive to the effects of dopamine than the normal striatum, although dopamine failed to elicit a response from an intact striatum opposite to a denervation by 6-OHDA. Following unilateral striatal electrolytic lesions (resulting in a stable response after 6–8 days) the rats exhibited ipsilateral asymmetry and circling after the apomorphine challenge. Again, the striata opposite to the lesion failed to mediate a response to dopamine. The contralateral responses to apomorphine observed in animals lesioned with 6-OHDA were not enhanced when an electrolytic lesion was subsequently placed in the intact striatum, nor were the ipsilateral responses of lesioned rats to apomorphine enhanced when 6-OHDA was subsequently injected into the opposite striatum. All asymmetric and circling responses were sensitive to neuroleptics. Thus, it is concluded that a unilateral striatal lesion produced by 6-OHDA or electrolytic lesion can cause reduced functional dopaminergic activity in the opposing striatum. This dopaminergic hyposensitivity would facilitate a contralateral response initiated by hypersensitive mechanisms in the denervated striatum.