UNILATERAL NIGROSTRIATAL LESIONS INDUCE A BILATERAL INCREASE IN GLUTAMATE-DECARBOXYLASE MESSENGER-RNA IN THE RETICULAR THALAMIC NUCLEUS

The reticular thalamic nucleus consists of densely packed neurons cont aining the neurotransmitter GABA. It surrounds the lateral border of t he thalamus, has extensive reciprocal connections with thalamocortical neurons, and is thought to be involved in attentional processes. The reticular thalamic nucleus also receives direct and indirect inputs fr om the basal ganglia, suggesting that it may be involved in relaying m otor information to the thalamus and cortex. We examined the possibili ty that decreased dopaminergic transmission in the basal ganglia indir ectly affects the reticular thalamic nucleus. Rats .received unilatera l 6-hydroxydopamine lesions of the substantia nigra pars compacta and were killed two or three weeks after the lesion. Sections of the retic ular thalamic nucleus were processed for in situ hybridization histoch emistry at the single cell level with RNA probes for both isoforms of glutamate decarboxylase (M, 65,000: glutamate decarboxylase 65 and M(r ) 67,000: glutamate decarboxylase 67), the rate limiting enzyme of GAB A synthesis. Unilateral nigrostriatal dopaminergic lesions induced a t opographically specific, bilateral increase in glutamate decarboxylase 67 messenger RNA in neurons of the lateral and ventral reticular thal amic nucleus. A much smaller increase in glutamate decarboxylase 65 me ssenger RNA was observed which was significant only ipsilateral to the lesion. Short- (seven day) and long-term (eight month) treatments wit h the antipsychotic drug haloperidol, in regimens that preferentially block D-2 dopamine receptors, induced catalepsy and orofacial dyskines ia, respectively, but did not alter glutamate decarboxylase 67 messeng er RNA levels in the reticular thalamic nucleus. Thus, loss of dopamin ergic terminals, but not blockade of D, dopamine receptors, induced th e effects observed in the reticular thalamic nucleus. The results reve al a novel bilateral effect of unilateral dopamine depletion. In view of the role of the reticular thalamic nucleus in tremor and attentiona l processes, which are altered in Parkinson's disease, this effect may contribute to the clinical manifestations of nigrostriatal dopamine d epletion.