Effects of unilateral intracerebroventricular microinjections of cholecystokinin (CCK) on circling behavior of rats

Unilateral intracerebroventricular (ICV) injections of a high dose of CCK7 have been reported to elicit barrel rotations accompanied by contralateral postural asymmetry; there was no spontaneous locomotor activity other than barrel rolling. The aim of the present study was to investigate the effects of lower doses of CCK-peptides on circling behavior; it was reasoned that if ambulation was present following unilateral ICV administrations of lower doses of CCK, then the contralateral postural asymmetry previously reported might be expressed as contraversive circling. In the present study, spontaneous locomotor activity was observed following ICV injections of lower doses of CCK sulfated octapeptide (CCK8), desulfated CCK octapeptide (dCCK8) and CCK tetrapeptide (CCK4). As postulated, contraversive circling was induced by CCK8 (0.5-5000 ng, ICV); the two other CCK fragments, dCCK8 and CCK4, were inactive in this respect. In addition, the contraversive circling bias induced by CCK8 (5.0 ng, ICV) was attenuated by co-injections of the CCK antagonist proglumide (10 and 100 ng) and by intraperitoneal injections of the dopamine (DA) antagonist haloperidol (0.05 and 0.1 mg/kg, 45 min prior to ICV CCK8). These data suggest that the effect is medited by CCK receptors and through a facilitatory influence on central DA function.