CCK(B) antagonists protect against anxiety-related behaviour produced by ethanol withdrawal, measured using the elevated plus maze.
The effects of the CCK(B) antagonists, CAM1028 and CI988 and a CCK(A) antagonist, CAM1481, were studied on the anxiety-related behaviour produced by withdrawal from chronic ethanol treatment, using the elevated plus maze. Cessation of chronic ethanol administration produced a profile, in both mice and rats, consistent with increase in anxiety-related behaviour. In mice, SC administration of CAM1028 or CI988 reduced the decrease in the time spent on the open arms, the number of entries into these arms and the increases in the latencies to first open arm entry, after withdrawal from the ethanol treatment. The increases in stretched attend postures and head dips from the closed arms and the central square seen during the withdrawal phase, were also decreased by the CCK(B) antagonists, but the decreases in the number of rears and in general activity were unaffected. The doses of CAM1028 and CI988 tested were 0.1 and 1 mg/kg; for some of the withdrawal-induced changes in behaviour only the 1 mg/kg dose was effective. In contrast, the CCK(A) antagonist, CAM1481, at the same doses, had little effect on the anxiety-related behaviour produced by withdrawal from chronic ethanol treatment, although it did decrease the changes in the number of rears and the head dipping behaviour. In rats, the majority of the changes produced by withdrawal from chronic ethanol treatment were decreased by CAM1028 at 1 mg/kg, although the decreases in open arm entries, rearing behaviour and in overall activity were unaffected. CAM1028, CI988 and CAM1481 had no effects on the behaviour of control mice or rats in the plus-maze. The results show that CCK(B) antagonists were effective in decreasing the majority of the anxiogenic effects of withdrawal from chronic ethanol treatment.
Wilson
J
J
Department of Pharmacology, School of Medical Sciences, University Walk, Bristol, UK.
Watson
W P
WP
Little
H J
HJ
D000818:Animals; D001007:Anxiety / Q000517:prevention & control*; D004151:Dipeptides / Q000494:pharmacology; D000431:Ethanol / Q000009:adverse effects*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008536:Meglumine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D011985:Receptors, Serotonin / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*
C097931:CAM 1481; D004151:Dipeptides; D007211:Indoles; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D011985:Receptors, Serotonin; C065600:PD 135158; C065599:PD 134308; D000431:Ethanol; D008536:Meglumine