title: Facilitation of fear extinction by novelty depends on dopamine acting on D1-subtype dopamine receptors in hippocampus.
abstract: Extinction is the learned inhibition of retrieval. Recently it was shown that a brief exposure to a novel environment enhances the extinction of contextual fear in rats, an effect explainable by a synaptic tagging-and-capture process. Here we examine whether this also happens with the extinction of another fear-motivated task, inhibitory avoidance (IA), and whether it depends on dopamine acting on D1 or D5 receptors. Rats were trained first in IA and then in extinction of this task. The retention of extinction was measured 24 h later. A 5-min exposure to a novel environment 30 min before extinction training enhanced its retention. Right after exposure to the novelty, animals were given bilateral intrahippocampal infusions of vehicle (VEH), of the protein synthesis inhibitor anisomycin, of the D1/D5 dopaminergic antagonist SCH23390, of the PKA inhibitor Rp-cAMP or of the PKC inhibitor Gö6976, and of the PKA stimulator Sp-cAMP or of the PKC stimulator PMA. The novelty increased hippocampal dopamine levels and facilitated the extinction, which was inhibited by intrahippocampal protein synthesis inhibitor anisomysin, D1/D5 dopaminerdic antagonist SCH23390, or PKA inhibitor Rp-cAMP and unaffected by PKC inhibitor Gö6976; additionally, the hippocampal infusion of PKA stimulator Sp-cAMP reverts the effect of D1/D5 dopaminergic antagonist SCH 23390, but the infusion of PKC stimulator PMA does not. The results attest to the generality of the novelty effect on fear extinction, suggest that it relies on synaptic tagging and capture, and show that it depends on hippocampal dopamine D1 but not D5 receptors.
authors.affiliation: Stress, Memory and Behavior Laboratory, Federal University of Pampa, 97500-970, Uruguaiana, RS, Brazil; and.
authors.forename: Jefferson
authors.initials: J
authors.lastname: Menezes
authors.affiliation: Stress, Memory and Behavior Laboratory, Federal University of Pampa, 97500-970, Uruguaiana, RS, Brazil; and.
authors.forename: Niége
authors.initials: N
authors.lastname: Alves
authors.affiliation: Stress, Memory and Behavior Laboratory, Federal University of Pampa, 97500-970, Uruguaiana, RS, Brazil; and.
authors.forename: Sidnei
authors.initials: S
authors.lastname: Borges
authors.affiliation: Stress, Memory and Behavior Laboratory, Federal University of Pampa, 97500-970, Uruguaiana, RS, Brazil; and.
authors.forename: Rafael
authors.initials: R
authors.lastname: Roehrs
authors.affiliation: Memory Center, Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul (PUCRS), 90610-000, Porto Alegre, RS, Brazil.
authors.forename: Jociane
authors.initials: J
authors.lastname: de Carvalho Myskiw
authors.affiliation: Memory Center, Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul (PUCRS), 90610-000, Porto Alegre, RS, Brazil.
authors.forename: Cristiane Regina Guerino
authors.initials: CR
authors.lastname: Furini
authors.affiliation: Memory Center, Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul (PUCRS), 90610-000, Porto Alegre, RS, Brazil izquier@terra.com.br.
authors.forename: Ivan
authors.initials: I
authors.lastname: Izquierdo
authors.affiliation: Stress, Memory and Behavior Laboratory, Federal University of Pampa, 97500-970, Uruguaiana, RS, Brazil; and.
authors.forename: Pâmela B
authors.initials: PB
authors.lastname: Mello-Carpes
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000737:chemistry; D001522:Behavior, Animal; D001552:Benzazepines / Q000737:chemistry; D002227:Carbazoles / Q000737:chemistry; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000737:chemistry; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004298:Dopamine / Q000737:chemistry; D005108:Extinction, Psychological; D005239:Fear; D006624:Hippocampus / Q000378:metabolism*; D007858:Learning; D008297:Male; D008568:Memory; D008569:Memory Disorders / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D050641:Receptors, Dopamine D5 / Q000378:metabolism; D013312:Stress, Physiological; D013873:Thionucleotides / Q000737:chemistry; D013997:Time Factors
chemical_list: D001552:Benzazepines; D002227:Carbazoles; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D013873:Thionucleotides; C081021:Go 6976; D050641:Receptors, Dopamine D5; C016957:adenosine-3',5'-cyclic phosphorothioate; D000841:Anisomycin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D004298:Dopamine
keywords: behavioral tagging and capture; dopamine; inhibitory avoidance; modulation of extinction; novelty