Modification of nigral kainic acid-induced ipsilateral circling behaviour in the rat by neuroleptics and by contralateral caudate ablation.

Abstract

A study was performed to examine possible changes in excitatory amino acid sensitivity within the pars reticulata of the rat substantia nigra as a result of neuroleptic exposure. Unilateral application of 20 ng kainic acid into caudal regions of the pars reticulata resulted in ipsilateral circling behaviour. This activity was significantly reduced 7 days after administration of the depot neuroleptic fluphenazine decanoate, 10.0 mg/kg SC, or 1 h after pretreatment with haloperidol, 0.1-1.0 mg/kg IP. The inhibitory effect of 0.1 mg/kg haloperidol was unaffected by prior ablation of the ipsilateral striatum, which by itself had no effect on the kainate-induced response. However, contralateral caudate ablation 21 days prior to intra-nigral kainate resulted in a markedly enhanced response, although 0.1 mg/kg haloperidol appeared to retain its inhibitory action when tested in such animals. The experimental data suggest a compensatory role of contralateral striatal mechanisms in nigral kainate-induced ipsilateral circling behaviour in the rat. Furthermore, they demonstrate at least a modulatory role of central dopaminergic mechanisms in such elicited behaviour. This latter action may involve multiple basal ganglia sites or, more probably, occur in other brain areas such as the mesolimbic system.