A central cholinergic link in the cardiovascular effects of the benzodiazepine receptor partial inverse agonist FG 7142

• Published in: Behavioural brain research Vol. 74; no. 1; pp. 91 - 103
• Main Authors: Berntson, G.G., Hart, S., Ruland, S., Sarter, M.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 1996; Elsevier Science
• Subjects: 192 IgG-sapori; Acetylcholine lesion; Animals; Antibodies, Monoclonal - toxicity; Appetite Depressants - pharmacology; Atropine; Atropine - administration & dosage; Atropine - toxicity; Behavioral psychophysiology; Benzodiazepine; Biological and medical sciences; Blood pressure; Blood Pressure - drug effects; Blood Pressure - physiology; Carbachol; Carbachol - administration & dosage; Carbachol - toxicity; Carbolines - pharmacology; Cholinergic Agents - toxicity; FG 7142; Fundamental and applied biological sciences. Psychology; GABA-A Receptor Agonists; Gamma-aminobutyric acid; Heart period; Hemodynamics - drug effects; Humans; Immunotoxins - toxicity; Injections, Intraventricular; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - pharmacology; Muscarinic Antagonists - toxicity; N-Glycosyl Hydrolases; Neurotransmission and behavior; Parasympathetic Nervous System - anatomy & histology; Parasympathetic Nervous System - drug effects; Parasympathetic Nervous System - physiology; Parasympathomimetics - administration & dosage; Parasympathomimetics - toxicity; Prosencephalon - anatomy & histology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Sprague-Dawley; Ribosome Inactivating Proteins, Type 1; Saporins; Carbachol; Benzodiazepine; Atropine; Acetylcholine lesion; Gamma-aminobutyric acid; 192 IgG-sapori; Heart period; Blood pressure; FG 7142; Affect affectivity; Rat; Rodentia; Benzodiazepine receptor; Parasympathomimetic; Heart rate; Cholinergic receptor; Vertebrata; Carboline derivatives; Mammalia; Inverse agonist; Animal; Muscarinic receptor; Anxiety; Hemodynamics; Parasympatholytic; Brain (vertebrata)
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/0166-4328(95)00166-2

Previous work demonstrated that systemic administration of the benzodiazepine receptor (BZR) partial inverse agonist β-carboline FG 7142 (FG) augments the cardiovascular response to non-signal stimuli, similar to the effects of an aversive context. Analyses of the parasympathetic and sympathetic contributions to the effects of FG prompted the hypothesis that increases in the present experiments demonstrate: (a) intracerebroventricular (ICV) infusion of the cholinergic receptor agonist carbachol mimics the response-potentiating effects of FG; (b) this effect of carbachol was blocked by ICV co-administration of the muscarinic antagonist atropine; (c) ICV infusions of atropine blocked the potentiation of the cardioacceleratory response by systemically administered FG, but did not alter the basal response to the stimulus; and (d) 192 IgG-saporin-induced lesions of basal forebrain cholinergic neurons prevented the FG-induced potentiation of the cardioacceleratory response, again without altering the basal cardiac response. These data strongly support the hypothesis that the effects of FG on cardiac reactivity are mediated via an activation of central muscarinic cholinergic mechanisms.