Effect of chronic ceruletide treatment on dopaminergic neurotransmitters, receptors and their mRNAs in the striatum of rats with dyskinesia induced by iminodipropionitrile

Abstract

To clarify the mechanism of long-lasting ceruletide action, an analogue of cholecystokinin, in relieving the dyskinesia induced by the iminodipropionitrile (IDPN), we investigated the changes in dopaminergic neuronal system in the striatum. In the control rats, ceruletide had no significant effect on the concentrations of dopamine (DA), DOPAC or HVA or on the turnover of DA in the striatum. The concentration of DA was decreased and the turnover of DA [(DOPAC + HVA)/DA] was increased in the striatum of IDPN-treated rats. Chronic administration of ceruletide (160 μ g· kg −1·day −1 × 10days) increased DA concentration and decreased DA turnover only transiently Both. D 1 and D 2 receptors and their mRNAs were decreased in the striatum of rats given IDPN. After chronic ceruletide treatment, D 1 receptor rose to the control level for 3 days, while the D 2 receptor rose to a level 1.5 times the control level for 3 days. Even at the 7 days after chronic ceruletide treatment, D 2-R rose significantly as compared with the IDPN-treated rats. Both D 1 and D 2 receptor mRNAs were significantly increased for 3 days in the IDPN-treated rats. These observations indicate that the synthesis of DA receptors is increased by ceruletide treatment in the striatum of IDPN-treated rats. These changes in DA receptors and their mRNAs closely paralleled the changes in dyskinetic movement of the IDPN-treated rats after repeated daily administration of ceruletide, as previously reported. The parallel changes between the DA receptors and dyskinetic movement suggest that an up-regulation of DA receptors in the striatum corresponds with an improvement of dyskinesia in the IDPN-treated rats. Thus, the efficacy of ceruletide in treating the dyskinesia induced by IDPN may be related to the up-regulation of DA receptors in the striatum.