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

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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.

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Acknowledgments

We thank J. C. Aguiar and L. Argentin for their technical support.

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    Authors and Affiliations

    1. 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

      M. V. Fogaça, A. G. Fedoce, N. C. Ferreira-Junior, F. S. Guimarães & L. B. Resstel

    2. Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo (USP), Ribeirão Preto, Brazil

      M. V. Fogaça, A. G. Fedoce, N. C. Ferreira-Junior, F. S. Guimarães & L. B. Resstel

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    1. M. V. Fogaça
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    4. F. S. Guimarães
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    Correspondence to M. V. Fogaça or L. B. Resstel.

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    Procedures were conducted in conformity with the Brazilian Society of Neuroscience and Behavior guidelines for the care and use of laboratory animals, which are in compliance with international laws and politics. The local ethics committee approved the experimental procedures.

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    Authors do not declare any conflict of interest.

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    This study was supported by grants from CAPES, CNPq (470311/2012-6) and FAPESP (2012/17626-7 and 2012/09300-4). CAPES, CNPq, or FAPESP had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

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    M. V. Fogaça, A. G. Fedoce and N. C. Ferreira-Junior contributed equally to this work.

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    Fogaça, M.V., Fedoce, A.G., Ferreira-Junior, N.C. et al. Involvement of M1 and CB1 receptors in the anxiogenic-like effects induced by neostigmine injected into the rat prelimbic medial prefrontal cortex. Psychopharmacology 233, 1377–1385 (2016). https://doi.org/10.1007/s00213-016-4228-7

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    • DOI: https://doi.org/10.1007/s00213-016-4228-7

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