CCKB ANTAGONISTS PROTECT AGAINST ANXIETY-RELATED BEHAVIOR PRODUCED BYETHANOL WITHDRAWAL, MEASURED USING THE ELEVATED PLUS-MAZE

The effects of the CCKB antagonists, CAM1028 and CI988 and a CCKA anta gonist, CAM1481, were studied on the anxiety-related behaviour produce d by withdrawal from chronic ethanol treatment, using the elevated plu s maze. Cessation of chronic ethanol administration produced a profile , in both mice and rats, consistent with increase in anxiety-related b ehaviour. In mice, SC administration of CAM1028 or CI988 reduced the d ecrease 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 stretc hed attend postures and head dips from the closed arms and the central square seen during the withdrawal phase, were also decreased by the C CKB antagonists, but the decreases in the number of rears and in gener al activity were unaffected. The doses of CAM1028 and CI988 tested wer e 0.1 and 1 mg/kg; for some of the withdrawal-induced changes in behav iour only the 1 mg/kg dose was effective. In contrast, the CCKA antago nist, CAM1481, at the same doses, had little effect on the anxiety-rel ated behaviour produced by withdrawal from chronic ethanol treatment. although it did decrease the changes in the number of oars and the hea d 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 behaviou r and in overall activity were unaffected. CAM1028, CI988 and CAM1481 had no effects on the behaviour of control mice or rats in the plus-ma ze. The results show that CCKB antagonists were effective in decreasin g the majority of the anxiogenic effects of withdrawal from chronic et hanol treatment.