THE ALPHA-2 ANTAGONISTS IDAZOXAN AND RAUWOLSCINE BUT NOT YOHIMBINE ORPIPEROXAN ARE ANXIOLYTIC IN THE VOGEL LICK-SHOCK CONFLICT PARADIGM FOLLOWING INTRAVENOUS ADMINISTRATION

The alpha(2) agonist clonidine has been shown to be anxiolytic in a nu mber of preclinical anxiety models. Interestingly, intravenous infusio n of the g antagonists idazoxan at 10 mg/kg and rauwolscine at 2.24 mg /kg significantly disinhibited lick-shock conflict responding in rats similar to the alpha(2) agonist clonidine (0.022 mg/kg) and the benzod iazepine diazepam (0.5 mg/kg). However, the alpha(2) antagonists yohim bine and piperoxan, the alpha(2) agonists medetomidine, guanfacine, an d guanabenz, the non-specific alpha antagonist phentolamine, and the a lpha(1) antagonist prazosin did not disinhibit conflict responding in the Vogel lick-shock paradigm. In fact, yohimbine has been shown to be anxiogenic in both animals and man. This may be due to yohimbine's la ck of specificity and its ability to inhibit GABAergic release. In add ition, all of these agents, except idazoxan, did not increase water co nsumption in water deprived rats. Idazoxan (10 mg/kg) significantly de creased water consumption by 45%. Therefore, idazoxan increased confli ct responding for water reward at a dose (10 mg/kg) which also decreas ed water consumption in a non-conflict paradigm. These data suggest th at agents with selective antagonism at the g receptor site may be anxi olytic while agents with less specificity at this site such as yohimbi ne, piperoxan, and phentolamine are not anxiolytic.