IMPAIRMENT OF STRESS ADAPTIVE BEHAVIORS IN RATS BY THE CCKA RECEPTOR ANTAGONIST, DEVAZEPIDE

1 Cholecystokinin (CCK) is released during stress both in Limbic and h ypothalamic areas suggesting that CCK could participate in modulating neuroendocrine as well as behavioural responses to stress. 2 In this s tudy we have examined the effect of CCK receptor antagonists on the re tention of the immobility response to a forced-swim stress in rats. In this test, rats are forced to swim during 15 min (conditioning period ) and 24 h later, the duration of immobility is measured during a peri od of 5 min (re-test period). During the conditioning period rats disp lay a period of vigorous activity, followed by progressive inactivity. During the re-test period rats remain 70-80% of the time in an immobi le posture. 3 The CCKA receptor antagonist, devazepide (MK-329) but no t the CCKB receptor antagonist, L-365,260, administered s.c. immediate ly before the conditioning period, decreased the duration of acquired immobility during the re-test period. The effect of devazepide was pre vented by cholecystokinin octapeptide (CCK-8; 40 mu g kg(-1), s.c.) as well as by the selective glucocorticosteroid G(II) receptor agonist, dexamethasone (30 mu g kg(-1), s.c.). 4 Neither corticosterone nor ACT H plasma levels measured both after the re-test period and after the c onditioning period were modified by devazepide treatment. 5 The result s suggest a role for CCK in the behavioural adaptation to stress and i ndicate a relationship between CCK systems and glucocorticoids in the neuronal mechanisms involved in the acquisition of adaptive behaviours to stress.