Anxiogenic effect of central CCK administration is attenuated by chronic fluoxetine or ipsapirone treatment

The effect of chronic fluoxetine and ipsapirone treatment on the anxiogenic effect of centrally administered cholecystokinin (CCK) was studied in the social interaction test in male Sprague-Dawley rats. Intracerebroventricula r injection of unsulfated CCK-8 significantly decreased total interaction t ime and locomotor activity and caused some increase in selfgrooming and a r eduction in rearing behaviour in a familiar arena in low light conditions. The selective serotonin reuptake inhibitor antidepressant fluoxetine alone (5 mg/kg, i.p.) also had clear acute anxiogenic actions (decrease in total interaction time, locomotor activity, rearing, increase in selfgrooming) af ter single dosing, but all these effects were omitted after chronic (3 week s) treatment. In contrast, a single injection of the 5-HT1A receptor partia l agonist ipsapirone (5 mg/kg, i.p.) alone had only motor effects (decrease in selfgrooming and rearing), and these effects were preserved after chron ic treatment. Chronic fluoxetine treatment (5 mg/kg per day, 3 weeks) aboli shed the effects of CCK-8 (1 nmol/rat, i.c.v.). Chronic treatment with ipsa pirone (5 mg/kg per day, 3 weeks) partially attenuated the effects of CCK-8 (1 nmol/rat, i.c.v.). Our studies provide further evidence for a 5-HT/CCK interaction in the regulation of anxiety. (C) 1999 Elsevier Science Ltd. Al l rights reserved.