Analysis of the antagonistic effect of caerulein on amphetamine hyperactivity

Abstract

Caerulein (CLN), chemically related to cholecystokinin octapeptide (CCK-8), generally produces a short-lasting pharmacological effect (Folia Pharmacol. Japon., 81, p6, 1982). However, in rats pretreated with a combination of CLN (0.3-40 μg/kg, s.c.) and haloperidol (HLP, 001mg/kg, s.c.), a long-lasting antagonistic effect on amphetamine (AMP) hyperactivity was found. In brief, animals, pretreated with a combination of CLN and HLP and exposed to AMP on the first day, become less sensitive to AMP for 24 hr to 2 weeks depending on the dose of CLN, when ambulatory activities were measured in an open field of Hall’s type. Examination of the properties of this long-lasting effect showed that: 1) In animals treated with CLN and HLP, but without AMP on the first day, the susceptibility to AMP was not influenced on the next day. 2) When another peptide was substituted for CLN, the antagonistic effect could be sustained only by injecting higher doses of CCK-8 (l60μg/kg) but not by nonsulfated CLN or small doses of CCK-8 (40μg/kg). 3) The long-lasting change in AMP susceptibility could be achieved if chlorpromazine or sulpiride was employed instead ofHLP. However, α-blocking agents, phenoxybenzamine and yohimbine, could not produce the effect. 4) Apomorphine, nomifensine and tranylcypromine could not be substituted for AMP. These results show that injecting CLN together with HLP and AMP on the first day might be necessary to produce a long-lasting anti-AMP effect. The effect was also observed in vagotomized rats or after an intracerebroventricular injection of CLN (100, 1000ng). Injection of CLN (10, 100ng) into the nucleus accumbens produced no effect. These observations are discussed in relation to a possible mechanism.