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 benzodiazepine receptor (BZR) partial inverse agonist beta-carboline FG 7142 (FG) augments the cardiovascular response to non-signal stimuli, similar to the effects of an aversive context. Analysis of the parasympathetic and sympathetic contributions to the effects of FG prompted the hypothesis that increases in central cholinergic activity mediates the potentiation of the cardioacceleratory response by FG. Consistent with this hypothesis, 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.
Berntson
G G
GG
Department of Psychology and Neuroscience Program, Ohio State University, Columbus 43210, USA.
Hart
S
S
Ruland
S
S
Sarter
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D001067:Appetite Depressants / Q000494:pharmacology*; D001285:Atropine / Q000008:administration & dosage / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000008:administration & dosage / Q000633:toxicity; D002243:Carbolines / Q000494:pharmacology*; D018678:Cholinergic Agents / Q000633:toxicity; D058785:GABA-A Receptor Agonists; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D000922:Immunotoxins / Q000633:toxicity; D007276:Injections, Intraventricular; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D009699:N-Glycosyl Hydrolases; D010275:Parasympathetic Nervous System / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D010277:Parasympathomimetics / Q000008:administration & dosage / Q000633:toxicity; D016548:Prosencephalon / Q000033:anatomy & histology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D001067:Appetite Depressants; D002243:Carbolines; D018678:Cholinergic Agents; D058785:GABA-A Receptor Agonists; D000922:Immunotoxins; D018727:Muscarinic Antagonists; D010277:Parasympathomimetics; D054789:Ribosome Inactivating Proteins, Type 1; C035874:FG 7142; D001285:Atropine; D002217:Carbachol; D009699:N-Glycosyl Hydrolases; D000076985:Saporins