Involvement of M1 and CB1 receptors in the anxiogenic-like effects induced by neostigmine injected into the rat prelimbic medial prefrontal cortex

• Published in: Psychopharmacology Vol. 233; no. 8; pp. 1377 - 1385
• Main Authors: Fogaça, M. V., Fedoce, A. G., Ferreira-Junior, N. C., Guimarães, F. S., Resstel, L. B.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2016
• Subjects: Animals; Anxiety - chemically induced; Anxiety - metabolism; Biomedical and Life Sciences; Biomedicine; Cholinesterase Inhibitors - administration & dosage; Cholinesterase Inhibitors - toxicity; Dose-Response Relationship, Drug; Injections, Intraventricular; Male; Muscarinic Antagonists - administration & dosage; Neostigmine - administration & dosage; Neostigmine - toxicity; Neurosciences; Original Investigation; Pharmacology/Toxicology; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Psychiatry; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1 - agonists; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB1 - metabolism; Receptor, Muscarinic M1 - agonists; Receptor, Muscarinic M1 - antagonists & inhibitors; Receptor, Muscarinic M1 - metabolism; Prelimbic medial prefrontal cortex; FAAH; Muscarinic; receptors; Acetylcholine; Anxiety; M1 receptors; Endocannabinoids; Cholinergic; CB; CB1 receptors
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-016-4228-7

The prelimbic (PL) medial prefrontal cortex is a brain region highly involved in the control of emotional responses, being modulated by several neurotransmitter systems, including the cholinergic and endocannabinoid. Activation of muscarinic type 1 (M1) receptors in the brain induces retrograde suppression of inhibition through the induction of endocannabinoid release, which, in turn, activates cannabinoid type 1 (CB 1 ) receptors. No study so far, however, has been conducted to investigate if the cholinergic and endocannabinoid systems interact in the PL to modulate anxiety-related behaviors. Thus, the present work aimed at verifying if intra-PL administration of neostigmine, an acetylcholinesterase inhibitor, would produce changes in anxiety-like behavior and if these effects are mediated by M1 and CB 1 receptor activation. Independent groups of animals received bilateral injections of vehicle, the M1 receptor antagonist pirenzepine (0.06, 0.6, and 6 nmol), the CB 1 receptor antagonist AM251 (0.1 nmol), or the fatty acid amide hydrolase (FAAH) enzyme inhibitor URB597 (1, 3, and 10 pmol), followed by vehicle or neostigmine (0.01, 0.1, and 1 nmol), and were submitted to the elevated plus-maze (EPM) test. Neostigmine (1 nmol) decreased open arm exploration of the maze. This anxiogenic-like effect was reproduced in another anxiety-related animal model, the light–dark box. Previous injection of pirenzepine or AM251 abolished this response in the EPM, whereas URB597 had no effect. These results suggest that CB 1 and M1 receptors interact in the PL to control anxiety-like behaviors.