ABSTRACT
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.
Subject(s)
Conditioning, Psychological , Fear/psychology , Prefrontal Cortex/metabolism , Receptor, Muscarinic M3/metabolism , Animals , Benzodiazepines/agonists , Cholinesterase Inhibitors/pharmacology , Conditioning, Psychological/drug effects , Emotions , Male , Muscarinic Antagonists/pharmacology , Parasympathetic Nervous System/drug effects , Prefrontal Cortex/drug effects , Rats , Rats, Wistar , Receptor, Muscarinic M3/drug effects , Synaptic Transmission/drug effectsABSTRACT
There is conflicting evidence concerning the role of the bed nucleus of the stria terminalis (BNST) in fear and anxiety-elicited behavior. Most of the studies investigating this role, however, employed irreversible lesions of this nucleus. The objective of the present study was to investigate the effects of an acute and reversible inactivation of the BNST in rats submitted to the Vogel conflict test (VCT) and contextual fear conditioning, two widely employed animal models that are responsive to prototypal anxiolytic drugs. Male Wistar rats were submitted to stereotaxic surgery to bilaterally implant cannulae into the BNST. Ten minutes before the test they received bilateral microinjections of cobalt chloride (CoCl(2)) (1 mM/100 nL), a nonselective synapse blocker. CoCl(2) produced anxiolytic-like effects in tests, increasing the number of punished licks in the VCT and decreasing freezing behavior and the increase in mean arterial blood pressure and heart rate of animals re-exposed to the context where they had received electrical foot shocks 24 h before. The results indicate that the BNST is engaged in behavioral responses elicited by punished stimuli and aversively conditioned contexts, reinforcing its proposed role in anxiety.
