Motor disturbances produced by intrastriatal injection of cyclic AMP and cyclic GMP.

Male albino rats were permanently cannulated bilaterally in the caudate/putamen nucleus and subsequently injected unilaterally with cyclic AMP or cyclic GMP. Both of these cyclic nucleotides failed to produce any obvious change in motor activity. The concomitant intrastriatal injection of carbachol and cyclic AMP resulted in enhancement of the carbachol-induced dyskinesias. Under similar conditions, cyclic GMP blocked the carbachol effects. The dibutyryl (db) derivatives of cyclic AMP and cyclic GMP both enhanced the carbachol-induced dyskinesias and both db cyclic nucleotides induced dyskinesias when injected intrastriatally alone. The concomitant intrastriatal injection of dopamine and carbachol resulted in a blockade of the carbachol-induced dyskinesias. Dopmaine had no effect on db cyclic AMP and db cyclic GMP dyskinesias. The db cyclic AMP effects characteristically involved the distal limb musculature, while the db cycle GMP effects largely involved the proximal limb and trunk muscles. The hypothesis for opposing action of cyclic AMP and cyclic GMP in the CNS and the discrepancy between the effects of intrastriatal injection of cyclic AMP and dopamine were discussed.