title: Fear extinction can be made state-dependent on peripheral epinephrine: role of norepinephrine in the nucleus tractus solitarius.
abstract: We investigate whether the extinction of inhibitory avoidance (IA) learning can be subjected to endogenous state-dependence with systemic injections of epinephrine (E), and whether endogenous norepinephrine (NE) and the nucleus tractus solitarius (NTS)→locus coeruleus→hippocampus/amygdala (HIPP/BLA) pathway participate in this. Rats trained in IA were submitted to two sessions of extinction 24 h apart: In the first, the animals were submitted to a training session of extinction, and in the second they were tested for the retention of extinction. Saline or E were given i.p. immediately after the extinction training (post-extinction training injections) and/or 6 min before the extinction test (pre-extinction test). Post-extinction training E (50 or 100 μg/kg) induced a poor retrieval of extinction in the test session of this task unless an additional E injection (50 μg/kg) was given prior to the extinction test. This suggested state-dependence. Muscimol (0.01 μg/side) microinfused into the NTS prior to the extinction test session blocked E-induced state-dependence. Norepinephrine (NE, 1 μg/side) infused bilaterally into NTS restores the extinction impairment caused by post-extinction training i.p. E. In animals with bilateral NTS blockade induced by muscimol, NE (1 μg/side) given prior to the extinction test into the CA1 region of the dorsal hippocampus or into the basolateral amygdala restored the normal extinction levels that had been impaired by muscimol. These results suggest a role for the NTS→locus coeruleus→HIPP/BLA pathway in the retrieval of extinction, as it has been shown to have in the consolidation of inhibitory avoidance and of object recognition learning.
authors.affiliation: Centro de Memória, Instituto do Cérebro, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga, 6690, 90610-600 Porto Alegre, RS, Brazil.
authors.forename: Jessica
authors.initials: J
authors.lastname: Rosa
authors.affiliation: Centro de Memória, Instituto do Cérebro, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga, 6690, 90610-600 Porto Alegre, RS, Brazil; Instituto Nacional de Neurociência Translacional, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Av. Ipiranga, 6690, 90610-600 Porto Alegre, RS, Brazil.
authors.forename: Jociane C
authors.initials: JC
authors.lastname: Myskiw
authors.affiliation: Centro de Memória, Instituto do Cérebro, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga, 6690, 90610-600 Porto Alegre, RS, Brazil; Instituto Nacional de Neurociência Translacional, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Av. Ipiranga, 6690, 90610-600 Porto Alegre, RS, Brazil.
authors.forename: Cristiane R G
authors.initials: CR
authors.lastname: Furini
authors.affiliation: Centro de Memória, Instituto do Cérebro, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga, 6690, 90610-600 Porto Alegre, RS, Brazil.
authors.forename: Gerson G
authors.initials: GG
authors.lastname: Sapiras
authors.affiliation: Centro de Memória, Instituto do Cérebro, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga, 6690, 90610-600 Porto Alegre, RS, Brazil; Instituto Nacional de Neurociência Translacional, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Av. Ipiranga, 6690, 90610-600 Porto Alegre, RS, Brazil. Electronic address: izquier@terra.com.br.
authors.forename: Ivan
authors.initials: I
authors.lastname: Izquierdo
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004837:Epinephrine / Q000008:administration & dosage / Q000502:physiology*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000502:physiology; D058785:GABA-A Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology; D009638:Norepinephrine / Q000008:administration & dosage / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*
chemical_list: D058785:GABA-A Receptor Agonists; D009118:Muscimol; D009638:Norepinephrine; D004837:Epinephrine
keywords: Central norepinephrine; Fear extinction; NTS→hippocampus/amygdala pathway; Peripheral epinephrine; State-dependence