Sequential changes of cholinergic and dopaminergic receptors in brains after 6-hydroxydopamine lesions of the medial forebrain bundle in rats

We studied sequential changes in muscarinic cholinergic receptors, high-aff inity choline uptake sites and dopamine D-2 receptors in the brain after 6- hydroxydopamine lesions of the medial forebrain bundle in rats. The animals were unilaterally lesioned in the medial forebrain bundle and the brains w ere analyzed at 1, 2, 4 and 8 weeks postlesion. [H-3] Quinuclidinylbenzilat e (QNB), [H-3]hemicholinum-3 (HC-3) and [H-3]raclopride were used to label muscarinic cholinergic receptors, high-affinity choline uptake sites and do pamine D-2 receptors, respectively. The degeneration of nigrostriatal pathw ay produced a transient decrease in [H-3]QNB binding in the parietal cortex of both ipislateral and contralateral sides at 2 and 8 weeks postlesion. [ H-3] QNB binding also showed a mild but insignificant decrease in the ipsil ateral striatum throughout the postlesion periods. No significant change wa s observed in the substantia nigra (SN) of both ipsilateral and contralater al sides throughout the postlesion periods. In contrast, [H-3]HC-3 binding showed no significant change in the parietal cortex of both ipsilateral and contralateral sides during the postlesion. However, [H-3]HC-3 binding was upregulated in the ipsilateral dorsolateral striatum throughout the postles ion periods. The ventromedial striatum also showed a significant increase i n [H-3]HC-3 binding at 1 week and 2 weeks postlesion. On the other hand, no significant change in [H-3]raclopride binding was found in the parietal co rtex of both ipsilateral and contralateral sides during the postlesion. [H- 3]Raclopride binding showed a conspicuous increase in the ipsilateral stria tum (35-52% of the sham-operated values in the lateral part and 39-54% in t he medial part) throughout the postlesion periods. In the contralateral sid e, a mild increase in [H-3]raclopride binding was also found in the striatu m (10-15% of the sham-operated values in the lateral part and 22% in the me dial part) after lesioning. However, a significant decline in [H-3]raclopri de binding was observed in the ipsilateral SN and ventral tegmental area du ring the postlesion. The present study indicates that 6-hydroxydopamine injection of medial fore brain bundle in rats can cause functional changes in high-affinity choline uptake site in the striatum, as compared with muscarinic cholinergic recept ors. Furthermore, our studies demonstrate an upregulation in dopamine D-2 r eceptors in the striatum and a decrease in the receptors in the SN and vent ral tegmental area after the 6-hydroxydopamine injection. Thus, these findi ngs provide further support for neurodegeneration of the nigrostriatal path way that occurs in Parkinson's disease.