Rats treated chronically with
reserpine develop spontaneous
oral dyskinesia. The present study examined the development of the
oral dyskinesia during the course of
reserpine treatment, and its persistence after termination of treatment. Rats were injected with either
reserpine (1 mg/kg, s.c.) or vehicle once daily for 4 days and then every other day for 6 weeks.
Oral dyskinesia developed rapidly, reaching a maximal level after 3 days. It persisted at a maximal level for up to 20 days after termination of
reserpine treatment, and continued to persist above control level for at least 60 days. The
reserpine-treated rats also exhibited stereotypy in response to acute injection of the D1-selective agonist
SKF-38393 (10 mg/kg), which was not observed in control rats. In contrast to the
oral dyskinesia, this altered sensitivity to
SKF-38393 returned to normal within 20 days after terminating the
reserpine treatment, suggesting that these two behavioral responses involve different neural mechanisms. Quantitative autoradiographic measurement of
dopamine receptor subtypes revealed that both D1 and D2 receptors were increased in the caudate-putamen (Cpu) and nucleus accumbens. Only the increase in D2 receptor density in the CPu correlated with the persistence of the
oral dyskinesia; both changes persisted following termination of the
reserpine treatment, and their magnitude was less at 60 days than at 1 and 20 days post-treatment. These results may have important implications for
tardive dyskinesia.