title: Angiotensin II's role in sodium lactate-induced panic-like responses in rats with repeated urocortin 1 injections into the basolateral amygdala: amygdalar angiotensin receptors and panic.
abstract: Rats treated with three daily urocortin 1 (UCN) injections into the basolateral amygdala (BLA; i.e., UCN/BLA-primed rats) develop prolonged anxiety-associated behavior and vulnerability to panic-like physiological responses (i.e., tachycardia, hypertension and tachypnea) following intravenous infusions of 0.5 M sodium lactate (NaLac, an ordinarily mild interoceptive stressor). In these UCN-primed rats, the osmosensitive subfornical organ (SFO) may be a potential site that detects increases in plasma NaLac and mobilizes panic pathways since inhibiting the SFO blocks panic following NaLac in this model. Furthermore, since SFO neurons synthesize angiotensin II (A-II), we hypothesized that the SFO projects to the BLA and releases A-II to mobilizing panic responses in UCN/BLA-primed rats following NaLac infusions. To test this hypothesis, rats received daily bilateral injections of UCN or vehicle into the BLA daily for 3 days. Five to seven days following the intra-BLA injections, we microinjected either the nonspecific A-II type 1 (AT1r) and 2 (AT2r) receptor antagonist saralasin, or the AT2r-selective antagonist PD123319 into the BLA prior to the NaLac challenge. The UCN/BLA-primed rats pre-injected with saralasin, but not PD123319 or vehicle, had reduced NaLac-induced anxiety-associated behavior and panic-associated tachycardia and tachypnea responses. We then confirmed the presence of AT1rs in the BLA using immunohistochemistry which, combined with the previous data, suggest that A-II's panicogenic effects in the BLA is AT1r dependent. Surprisingly, the SFO had almost no neurons that directly innervate the BLA, which suggests an indirect pathway for relaying the NaLac signal. Overall these results are the first to implicate A-II and AT1rs as putative neurotransmitter-receptors in NaLac induced panic-like responses in UCN/BLA-primed rats.
authors.affiliation: Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, United States.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Johnson
authors.forename: Tammy J
authors.initials: TJ
authors.lastname: Sajdyk
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Fitz
authors.forename: Mathew W
authors.initials: MW
authors.lastname: Hale
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lowry
authors.forename: Anders
authors.initials: A
authors.lastname: Hay-Schmidt
authors.forename: Anantha
authors.initials: A
authors.lastname: Shekhar
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002772:Cholera Toxin / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009434:Neural Pathways / Q000502:physiology; D010146:Pain / Q000139:chemically induced; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000378:metabolism*; D019354:Sodium Lactate / Q000633:toxicity; D054832:Urocortins / Q000008:administration & dosage*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D011945:Receptors, Angiotensin; D054832:Urocortins; D000804:Angiotensin II; C073402:PD 123319; D002772:Cholera Toxin; D019354:Sodium Lactate