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

Author(s)

Fogaca, M. V. ^{[1, 2]} ; Fedoce, A. G. ^{[1, 2]} ; Ferreira-Junior, N. C. ^{[1, 2]} ; Guimares, F. S. ^{[1, 2]} ; Resstel, L. B. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPN, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo FMRP USP, Dept Pharmacol, Med Sch Ribeirao Preto, 3900 Bandeirantes Ave, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Psychopharmacology; v. 233, n. 8, p. 1377-1385, APR 2016.
• Web of Science Citations: 2

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. (AU)

• FAPESP's process: 12/17626-7 - Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/09300-4 - Bed nucleus of the stria terminalis noradrenergic system modulates contextual fear conditionig: possible interaction with CRF and glutamatergic and nitrergic neurotransmission
• Grantee: Leonardo Resstel Barbosa Moraes
• Support Opportunities: Regular Research Grants