Intracerebroventricular administration of cholecystokinin reduces stereotypy in dopamine-supersensitive rats.

Cholecystokinin (CCK-8) coexists with dopamine in some neurons and modulates dopaminergic neurotransmission. In the present study we determined the effect of CCK-8 on stereotyped behavior in supersensitive dopaminergic system. Adult male Wistar rats, weighing 200-250 g, were used. Dopaminergic supersensitivity was induced by long-term haloperidol (HAL) treatment (30 days: 1.0 mg/kg twice a day). Seventy-two hours after HAL withdrawal animals received CCK-8 (14.5 nmol/5 microliters) or saline intracerebroventricularly (icv) before being tested for apomorphine (APO, 0.6 mg/kg, sc)-induced stereotyped behavior. Experimental groups were: long-term HAL-treated rats that received saline (HSAL, N = 9) or CCK-8 (HCCK, N = 11) icv and long-term saline-treated rats that received CCK-8 (SCCK, N = 9) or saline (SSAL, N = 8) icv. As expected, HSAL rats showed statistically significant higher stereotypy scores than SSAL rats (42 +/- 1.7 vs 31 +/- 1.6; P < 0.05) and CCK-8 significantly reduced stereotyped behavior in supersensitive rats (42 +/- 1.7 vs 37 +/- 1.5; P < 0.05). These results show that CCK-8 icv reduces stereotypy in dopaminergic-supersensitive rats, and suggest that the dopamine supersensitivity phenomenon can be modulated by CCK-8.