title: Involvement of M1 and CB₁ receptors in the anxiogenic-like effects induced by neostigmine injected into the rat prelimbic medial prefrontal cortex.
abstract: 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 (CB1) 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 CB1 receptor activation. Independent groups of animals received bilateral injections of vehicle, the M1 receptor antagonist pirenzepine (0.06, 0.6, and 6 nmol), the CB1 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 CB1 and M1 receptors interact in the PL to control anxiety-like behaviors.
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto-University of São Paulo (FMRP-USP), 3900 Bandeirantes Avenue, Monte Alegre, Ribeirão Preto, SP, Brazil, 14049-900. manoelafogaca@usp.br.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo (USP), Ribeirão Preto, Brazil. manoelafogaca@usp.br.
authors.forename: M V
authors.initials: MV
authors.lastname: Fogaça
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto-University of São Paulo (FMRP-USP), 3900 Bandeirantes Avenue, Monte Alegre, Ribeirão Preto, SP, Brazil, 14049-900.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo (USP), Ribeirão Preto, Brazil.
authors.forename: A G
authors.initials: AG
authors.lastname: Fedoce
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto-University of São Paulo (FMRP-USP), 3900 Bandeirantes Avenue, Monte Alegre, Ribeirão Preto, SP, Brazil, 14049-900.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo (USP), Ribeirão Preto, Brazil.
authors.forename: N C
authors.initials: NC
authors.lastname: Ferreira-Junior
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto-University of São Paulo (FMRP-USP), 3900 Bandeirantes Avenue, Monte Alegre, Ribeirão Preto, SP, Brazil, 14049-900.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo (USP), Ribeirão Preto, Brazil.
authors.forename: F S
authors.initials: FS
authors.lastname: Guimarães
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto-University of São Paulo (FMRP-USP), 3900 Bandeirantes Avenue, Monte Alegre, Ribeirão Preto, SP, Brazil, 14049-900. leoresstel@yahoo.com.br.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo (USP), Ribeirão Preto, Brazil. leoresstel@yahoo.com.br.
authors.forename: L B
authors.initials: LB
authors.lastname: Resstel
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D009388:Neostigmine / Q000008:administration & dosage* / Q000633:toxicity; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043643:Receptor, Muscarinic M1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D043884:Receptor, Cannabinoid, CB1; D043643:Receptor, Muscarinic M1; D009388:Neostigmine
keywords: Acetylcholine; Anxiety; CB1 receptors; Cholinergic; Endocannabinoids; FAAH; M1 receptors; Muscarinic; Prelimbic medial prefrontal cortex