EVIDENCE FOR POTENTIATION BY CCK ANTAGONISTS OF THE EFFECT OF CHOLECYSTOKININ-OCTAPEPTIDE IN THE ELEVATED PLUS-MAZE

Systemic treatment with cholecystokinin octapeptide (CCK-8, 2.5-10 mu g/kg, s.c.), a non-selective CCK agonist, decreased the exploratory activity of mice in an elevated plus-maze. At higher doses (5-10 mu g/kg) CCK-8 reduced the frequency of rearing, but only 10 mu g/kg of CCK-8 significantly inhibited the number of line crossings in the open-field test. A preferential CCKB antagonist L-365,260 (1 and 100 mu g/kg, i.p.) and a non-selective CCK antagonist proglumide (0.1-1 mu g/kg, i.p.) potentiated the anti-exploratory effect of CCK-8 (2.5 mu g/kg). Devazepide, a preferential CCKA antagonist, only at a high dose (100 mu g/kg) tended to increase the action of CCK-8 in the plus-maze. However, the concomitant treatment of CCK-8 with L-365,260 and proglumide, differently from devazepide, also suppressed the locomotor activity in the open-field test. Therefore, it is likely that the potentiation by CCK antagonists of the anti-exploratory effect of CCK-8 is related to the suppression of motor activity. This peculiar interaction between CCK-8 and CCK antagonists could be explained in the light of the opposite role of CCKA and CCKB receptors in the regulation of motor activity in mice.