title: Effects of inactivation of serotonergic neurons of the median raphe nucleus on learning and performance of contextual fear conditioning.
abstract: Several studies have shown that the median raphe nucleus (MRN) is involved in anxiety. However, no study assessed the role of 5-HT mechanisms of MRN in both freezing and fear-potentiated startle (FPS) within a single form of conditioned learning. In this work we examined the effects of neurotoxic lesions of the MRN with NMDA on freezing and FPS of rats submitted to a contextual fear conditioning paradigm, in which they were tested in the same chamber where they received foot-shocks 24 h before. Compared to controls NMDA-injected rats showed a reduction of freezing and FPS in response to contextual cues. Next, we examined the effects of stimulation of 5-HT1A somatodendritic autoreceptors of the MRN with local injections of 8-OH-DPAT either before training or testing sessions conducted 2 or 24 h post-conditioning. Pre-training injections of 8-OH-DPAT intra-MRN reduced both freezing and FPS whereas post-training injections reduced only freezing to the aversive context without changing the FPS. Thus, freezing is easily disrupted by post-training MRN injections of 8-OH-DPAT while memory for FPS remained unchanged. It is proposed that the consolidation of contextual conditioned fear promoting freezing takes place through a slow mechanism of transference of information through 5-HT mechanisms of the MRN-hippocampus pathway. On the other hand, a rapid fear conditioning process operates for FPS, probably through other pathways.
authors.affiliation: Laboratório de Psicobiologia, FFCLRP, Campus USP, Av. Bandeirantes 3900, 14049-901, Ribeirão Preto, SP, Brazil.
authors.forename: Karina Genaro
authors.initials: KG
authors.lastname: Borelli
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Gárgaro
authors.forename: Júlia Maria
authors.initials: JM
authors.lastname: dos Santos
authors.forename: Marcus Lira
authors.initials: ML
authors.lastname: Brandão
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001008:Anxiety Disorders / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003714:Denervation; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008297:Male; D016202:N-Methylaspartate; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins; D011149:Pons / Q000166:cytology / Q000378:metabolism*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D016202:N-Methylaspartate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin