EFFECTS OF THE CCKB ANTAGONIST L-365,260 ON BENZODIAZEPINE WITHDRAWAL-INDUCED HYPOPHAGIA IN RATS

The effect of the selective CCKB antagonist L-365, 260 on chlordiazepo xide (CDP) withdrawal-induced hypophagia was assessed in two related s tudies in rats pretreated for 21 days with CDP at doses escalated from 10 to 30 mg/kg per day (b.i.d.). L-365, 260 was studied at doses from 0.001 to 10 mg/kg (b.i.d.). There was no evidence that L-365, 260 at any dose alleviated CDP withdrawal-induced hypophagia. These data cont rast with reports that CCKB antagonists alleviate behavioural benzodia zepine (BZ) withdrawal symptoms considered to be indicative of ''anxio genesis''. Presumably, such positive effects of CCKB antagonists are d ue to ''functional antagonism'', with enhanced anxiety during BZ withd rawal being attenuated by anxiolytic actions of CCKB antagonists. Coll ectively, studies with CCKB antagonists and other agents involving a n umber of different BZ withdrawal signs suggest that BZ withdrawal is a heterogeneous syndrome, with various different underlying mechanisms. CCKB antagonists appear to alleviate only a subset of possible BZ wit hdrawal signs.