Gabaergic-benzodiazepine system is involved in the crotoxin-induced anxiogenic effect

The behavioral effects of crotoxin (CTX), the major component of Crotalus d urissus terrificus venom, were studied in rats submitted to the open field, holeboard, and social interaction tests. CTX (100, 250, and 500 mu g/kg, I P) was administered 2 h before the tests. In the open field, CTX reduced am bulation (250 mu g/kg) and rearing (250 and 500 mu g/kg) and increased groo ming (100 and 250 mu g/kg) and freezing (250 mu g/kg). In the holeboard and social interaction, all the CTX doses evaluated decreased, respectively, h ead dip and head dipping, and social interaction time. The CTX-induced beha vioral alterations could be attributed to its neuromuscular transmission bl ockade, but this possibility was ruled out because CTX (250 and 500 mu g/kg , IP, 2 h before the rotarod test) was unable to modify the rotarod perform ance of rats. The involvement of the benzodiazepine receptor in the CTX-ind uced behavioral alterations was investigated through the pretreatment (30 m in before the tests, IP) of the animals with diazepam (1.2 mg/kg), or fluma zenil (4 and 10 mg/kg). Both diazepam and flumazenil antagonized the CTX in duced behavioral alterations in the open field, holeboard, and social inter action tests. This study demonstrated that: (1) CTX is an anxiogenic compou nd; and (2) the gabaergic-benzodiazepine system may play a role in the CTX- induced anxiogenic effect. (C) 1999 Elsevier Science Inc.