title: GABAA receptor endocytosis in the basolateral amygdala is critical to the reinstatement of fear memory measured by fear-potentiated startle.
abstract: Reinstatement represents a phenomenon that may be used to model the effects of retraumatization observed in patients with posttraumatic stress disorder (PTSD). In this study, we found intraperitoneal injection of the β-adrenergic receptor antagonist propranolol (10 mg/kg) 1 h before reinstatement training attenuated reinstatement of fear memory in rats. Conversely, reinstatement was facilitated by intra-amygdalar administration of β-adrenergic receptor agonist isoproterenol (Iso; 2 μg per side) 30 min before reinstatement training. The frequency and amplitude of the miniature IPSC (mIPSC) and the surface expression of the β3 and γ2 subunits of the GABA(A) receptor (GABA(A)R) were significantly lower in reinstated than in extinction rats, whereas the AMPA/NMDA ratio and the surface expression of GluR1 and GluR2 in the amygdala did not differ between groups. In amygdala slices, Iso-induced decrease in the surface β3 subunit of GABA(A) receptor was blocked by a Tat-conjugated dynamin function-blocking peptide (Tat-P4) pretreatment (10 μm for 30 min). By contrast, Tat-scramble peptide had no effect. Intravenous injection (3 μmol/kg) or intra-amygdalar infusion (30 pmol per side) of Tat-P4 interfered with reinstatement. Reinstatement increased the association between protein phosphatase 2A (PP2A) and the β3 subunit of the GABA(A)R, which was abolished by PP1/PP2A inhibitors okadaic acid and calyculin A. These results suggest the involvement of β-adrenergic receptor activation and GABA(A) receptor endocytosis in the amygdala for the reinstatement in fear memory.
authors.affiliation: Department of Pharmacology, Center for Gene Regulation and Signal Transduction Research, National Cheng-Kung University, Tainan, Taiwan 701.
authors.forename: Hui-Ching
authors.initials: HC
authors.lastname: Lin
authors.forename: Yu-Chou
authors.initials: YC
authors.lastname: Tseng
authors.forename: Sheng-Chun
authors.initials: SC
authors.lastname: Mao
authors.forename: Po-See
authors.initials: PS
authors.lastname: Chen
authors.forename: Po-Wu
authors.initials: PW
authors.lastname: Gean
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019921:Biotinylation; D003214:Conditioning, Classical / Q000187:drug effects; D034281:Dynamins / Q000037:antagonists & inhibitors; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects; D005239:Fear; D047468:Immunoprecipitation; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012201:Reward; D009435:Synaptic Transmission / Q000187:drug effects; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D018691:Excitatory Amino Acid Antagonists; D011963:Receptors, GABA-A; D011993:Recombinant Fusion Proteins; C526890:TAT-PTEN fusion protein; D054322:tat Gene Products, Human Immunodeficiency Virus; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D011433:Propranolol; D051059:PTEN Phosphohydrolase; D034281:Dynamins; D014633:Valine; D007545:Isoproterenol