Effects of sulfated cholecystokinin octapeptide and cholecystokinin tetrapeptide in rat behavior after blockade of nitric oxide synthase by L-NAME.

This study was conducted to determine what, if any, role L-NAME (inhibitor of nitric oxide synthase) plays in the behavioral effects induced by sulfated cholecystokinin octapeptide CCK-8) and cholecystokinin tetrapeptide (CCK-4) in adult male rats. The motility, stereotypy, anxiety, extinction of conditioned avoidance responses and recall of passive avoidance behavior were estimated. CCK-8 (but not CCK-4) injected intracerebroventricularly (icv) at the dose 0.1 nmole decreased of locomotor activity in the "open field" test. Administration of CCK-8 intensified stereotypy evoked by apomorphine (1 mg/kg, i.p.). The CCK-4 was ineffective in this test. Both, CCK-8 and CCK-4 did not make any significant differences in passive avoidance behavior. Examine the influence of CCK-8 and CCK-4 on the extinction of conditioned avoidance responses (CAR) proved that both peptide tended to facilitate extinction of CAR's. CCK-8 and CCK-4 induced anxiogenic-like effect in the elevated 'plus' maze behavior. Application of L-NAME alone (50 nmole,-icv) decreased of motility and stereotypy behavior in control rats. It was ineffective in a passive avoidance behavior and extinction of CAR's. In elevated 'plus' maze behavior injection of L-NAME, similarly to cholecystokinin, induced anxiogenic-like effect. L-NAME induced of motility decreases in the "open field" test were blocked by injection of CCK-8 and CCK-4. Our results indicate that observed behavioral activity of CCK-8 and CCK-4 (except of influence on motility) is probably independent of NO concentration in the brain.