PMID- 26518024 OWN - NLM STAT- MEDLINE DCOM- 20160808 LR - 20191210 IS - 1432-2072 (Electronic) IS - 0033-3158 (Linking) VI - 233 IP - 2 DP - 2016 Jan TI - M3 muscarinic receptor in the ventral medial prefrontal cortex modulating the expression of contextual fear conditioning in rats. PG - 267-80 LID - 10.1007/s00213-015-4109-5 [doi] AB - RATIONALE: Basal forebrain cholinergic neurons modulate the activation of cortical neurons by several stimuli such as fear and anxiety. However, the role of the muscarinic receptor in the medial prefrontal cortex (MPFC) in the modulation of the conditioned emotional response (CER) evoked in the model contextual conditioned fear remains unclear. OBJECTIVES: The objective of this study is to test the hypothesis that inhibition of the muscarinic receptor in ventral MPFC modulates CER observed during animal's re-exposure to the aversive context. METHODS: Rats implanted with cannulae aimed at the prelimbic (PL) or the infralimbic (IL) were submitted to a high-intensity contextual fear conditioning protocol. Before the test session, they received microinjections of the hemicholinium (choline reuptake blocker), atropine (muscarinic antagonist), J104129 fumarate (M1-M3 muscarinic antagonists), pirenzepine (M1 muscarinic antagonist), neostigmine (inhibitor acetylcholinesterase enzyme), or the systemic administration of the FG7142 (inverse benzodiazepine agonist). Additional independent groups received the neostigmine or FG7142 before the ineffective doses of J104129 fumarate in the low-intensity protocol of contextual fear conditioning. RESULTS: In the high-intensity protocol, the administration of hemicholinium (1 nmol), atropine (0.06-6 nmol), J104129 fumarate (6 nmol), or pirenzepine (6 nmol) attenuated the expression of CER in rats. However, in the low-intensity protocol, only J10129 fumarate (0.06 nmol) reduced the expression of the CER. Finally, neostigmine (0.1-1 nmol) or FG7142 (8 mg/Kg) increased CER expression, an effect inhibited by the low dose of the J10129 fumarate. CONCLUSIONS: These results indicated that the blockade of M3 muscarinic receptor in the vMPFC attenuates the CER expression. FAU - Fedoce, A G AU - Fedoce AG AD - Department of Pharmacology, Ribeirao Preto School of Medicine, University of Sao Paulo, Av. Bandeirantes, 3900, CEP: 14049-900, Ribeirao Preto, SP, Brazil. AD - Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Brazil. FAU - Ferreira-Junior, N C AU - Ferreira-Junior NC AD - Department of Pharmacology, Ribeirao Preto School of Medicine, University of Sao Paulo, Av. Bandeirantes, 3900, CEP: 14049-900, Ribeirao Preto, SP, Brazil. AD - Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Brazil. FAU - Reis, D G AU - Reis DG AD - Department of Pharmacology, Ribeirao Preto School of Medicine, University of Sao Paulo, Av. Bandeirantes, 3900, CEP: 14049-900, Ribeirao Preto, SP, Brazil. AD - Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Brazil. FAU - Correa, F M A AU - Correa FM AD - Department of Pharmacology, Ribeirao Preto School of Medicine, University of Sao Paulo, Av. Bandeirantes, 3900, CEP: 14049-900, Ribeirao Preto, SP, Brazil. FAU - Resstel, L B M AU - Resstel LB AD - Department of Pharmacology, Ribeirao Preto School of Medicine, University of Sao Paulo, Av. Bandeirantes, 3900, CEP: 14049-900, Ribeirao Preto, SP, Brazil. leoresstel@yahoo.com.br. AD - Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Brazil. leoresstel@yahoo.com.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151031 PL - Germany TA - Psychopharmacology (Berl) JT - Psychopharmacology JID - 7608025 RN - 0 (Cholinesterase Inhibitors) RN - 0 (Muscarinic Antagonists) RN - 0 (Receptor, Muscarinic M3) RN - 12794-10-4 (Benzodiazepines) SB - IM MH - Animals MH - Benzodiazepines/agonists MH - Cholinesterase Inhibitors/pharmacology MH - *Conditioning, Psychological/drug effects MH - Emotions MH - Fear/*psychology MH - Male MH - Muscarinic Antagonists/pharmacology MH - Parasympathetic Nervous System/drug effects MH - Prefrontal Cortex/drug effects/*metabolism MH - Rats MH - Rats, Wistar MH - Receptor, Muscarinic M3/drug effects/*metabolism MH - Synaptic Transmission/drug effects OTO - NOTNLM OT - Acetylcholine OT - Anxiety OT - Conditioned emotional response OT - Medial prefrontal cortex OT - Muscarinic receptor EDAT- 2015/11/01 06:00 MHDA- 2016/08/09 06:00 CRDT- 2015/11/01 06:00 PHST- 2015/03/25 00:00 [received] PHST- 2015/10/03 00:00 [accepted] PHST- 2015/11/01 06:00 [entrez] PHST- 2015/11/01 06:00 [pubmed] PHST- 2016/08/09 06:00 [medline] AID - 10.1007/s00213-015-4109-5 [pii] AID - 10.1007/s00213-015-4109-5 [doi] PST - ppublish SO - Psychopharmacology (Berl). 2016 Jan;233(2):267-80. doi: 10.1007/s00213-015-4109-5. Epub 2015 Oct 31.