Modulation of the extinction of two different fear-motivated tasks in three distinct brain areas

• Published in: Behavioural brain research 2012-06, Vol.232 (1), p.210-216
• Main Authors: Fiorenza, Natalia Gindri, Rosa, Jessica, Izquierdo, Ivan, Myskiw, Jociane C.
• Format: Article
• Language: English
• Subjects: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - administration & dosage; 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - pharmacology; 2-Amino-5-phosphonovalerate - administration & dosage; 2-Amino-5-phosphonovalerate - pharmacology; Adrenergic beta-Antagonists - pharmacology; Amygdala; Amygdala - drug effects; Animals; Avoidance Learning - drug effects; Benzazepines - administration & dosage; Benzazepines - pharmacology; Brain; CA1 Region, Hippocampal - physiology; Catheterization; Cortex (prefrontal); D-Serine; Dopamine; Dopamine Antagonists - administration & dosage; Dopamine Antagonists - pharmacology; Dopamine D1 receptors; Drugs; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - pharmacology; Extinction; Extinction, Psychological - drug effects; Fear - drug effects; Fear - psychology; Fear conditioning; Glutamic acid; Glutamic acid receptors (ionotropic); Hippocampus; Hippocampus - drug effects; Histamine; Histamine H2 Antagonists - administration & dosage; Histamine H2 Antagonists - pharmacology; Histamine H2 receptors; Histamine receptors; Male; Memory; Microinjections; Modulation of extinction; Motivation - drug effects; N-Methyl-D-aspartic acid receptors; NMDA receptors; Norepinephrine; Prefrontal Cortex - drug effects; Ranitidine; Ranitidine - adverse effects; Ranitidine - pharmacology; Rats; Rats, Wistar; Stimulants; timolol; Timolol - pharmacology
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2012.04.015

► We studied the effect of 8 modulatory treatments on 2 types of extinction. ► Treatments were given into hippocampus, amygdala and infralimbic prefrontal cortex. ► Extinction uses NMDA receptors and histamine H2 modulation in all these regions. ► Noradrenergic and dopaminergic modulation is more task- and region-selective. ► The findings bear on the use of extinction for treating PTSD and related disorders. 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 (50μg/side) and the histamine methyl-transferase inhibitor SKF9188 (12.5μg/side) enhanced, and the NMDA antagonist amino-phosphonopentanoate (5μg/side) and the H2 histamine receptor antagonist ranitidine (17.5μg/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 (1μg/side), the β-adrenoceptor antagonist timolol (1μg/side), the D1 dopamine receptor agonist SKF38393 (12.5μg/side) and the D1 antagonist SCH23390 (1.5μg/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.