title: Modulation of the extinction of two different fear-motivated tasks in three distinct brain areas.
abstract: The hippocampus, basolateral amygdala and ventromedial prefrontal cortex participate in the extinction of inhibitory avoidance and contextual fear conditioning. We studied the effect of drugs acting on receptors involved in synaptic modulation on extinction of both tasks. The drugs were given bilaterally right after the first of two sessions of extinction in each task through cannulae implanted into the mentioned areas. The doses used are known to influence memory consolidation of the original tasks. Their effects were evaluated on a second extinction session 24h later, and assumed to result from influences on the consolidation of extinction. The glutamate NMDA receptor stimulant d-serine (50 μg/side) and the histamine methyl-transferase inhibitor SKF9188 (12.5 μg/side) enhanced, and the NMDA antagonist amino-phosphonopentanoate (5 μg/side) and the H2 histamine receptor antagonist ranitidine (17.5 μg/side) inhibited, extinction of both tasks regardless of the region into which they were administered. Thus, glutamate NMDA receptors are involved in the consolidation of extinction of both tasks, and histamine H2 receptors modulate that process in all areas studied. Norepinephrine (1 μg/side), the β-adrenoceptor antagonist timolol (1 μg/side), the D1 dopamine receptor agonist SKF38393 (12.5 μg/side) and the D1 antagonist SCH23390 (1.5 μg/side) also affected extinction of both tasks, but their effects varied with the task and with the site of infusion, suggesting that extinction modulation by β- and D1 receptors is more complex. In conclusion, extinction of two different aversive tasks is modulatable by various systems, which bears upon the behavioral and pharmacological treatment of fear-motivated brain disorders.
authors.affiliation: Centro de Memoria, Instituto do Cerebro, Pontifical Catholic University of Rio Grande do Sul, and Instituto Nacional de Neurociência Translacional, Conselho Nacional de Desenvolvimento Científico e Tecnológico, 90610-000 Porto Alegre, RS, Brazil.
authors.forename: Natalia Gindri
authors.initials: NG
authors.lastname: Fiorenza
authors.forename: Jessica
authors.initials: J
authors.lastname: Rosa
authors.forename: Ivan
authors.initials: I
authors.lastname: Izquierdo
authors.forename: Jociane C
authors.initials: JC
authors.lastname: Myskiw
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage / Q000494:pharmacology; D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000502:physiology; D002404:Catheterization; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects / Q000523:psychology*; D006624:Hippocampus / Q000187:drug effects*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009042:Motivation / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects*; D011899:Ranitidine / Q000009:adverse effects / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013999:Timolol / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D006635:Histamine H2 Antagonists; C534628:SCH 23390; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D015763:2-Amino-5-phosphonovalerate; D013999:Timolol; D011899:Ranitidine