A CENTRAL CHOLINERGIC LINK IN THE CARDIOVASCULAR EFFECTS OF THE BENZODIAZEPINE RECEPTOR PARTIAL INVERSE AGONIST FG-7142

Previous work demonstrated that systemic administration of the benzodi azepine receptor (BZR) partial inverse agonist beta-carboline FG 7142 (FG) augments the cardiovascular response to non-signal stimuli, simil ar to the effects of an aversive context. Analyses of the parasympathe tic and sympathetic contributions to the effects of FG prompted the hy pothesis that increases in central cholinergic activity mediates the p otentiation of the cardioacceleratory response by FG. Consistent with this hypothesis, the present experiments demonstrate: (a) intracerebro ventricular (ICV) infusion of the cholinergic receptor agonist carbach ol mimics the response-potentiating effects of FG; (b) this effect of carbachol was blocked by ICV co-administration of the muscarinic antag onist atropine; (c) ICV infusions of atropine blocked the potentiation of the cardioacceleratory response by systemically administered FG, b ut did not alter the basal response to the stimulus; and (d) 192 IgG-s aporin-induced lesions of basal forebrain cholinergic neurons prevente d the FG-induced potentiation of the cardioacceleratory response, agai n without altering the basal cardiac response. These data strongly sup port the hypothesis that the effects of FG on cardiac reactivity are m ediated via an activation of central muscarinic cholinergic mechanisms .