Chronic inhibition of GABA synthesis in the bed nucleus of the stria terminalis elicits anxiety-like behavior

• Published in: Journal of psychopharmacology (Oxford) 2008-08, Vol.22 (6), p.633-641
• Main Authors: Sajdyk, TJ, Johnson, PL, Fitz, SD, Shekhar, A.
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Amygdala (Brain); Animals; Antianxiety agents; Anxiety; Anxiety - chemically induced; Anxiety disorders. Neuroses; Biological and medical sciences; Blood Pressure - drug effects; Care and treatment; Chemical synthesis; Dosage and administration; GABA; GABA Antagonists - metabolism; gamma-Aminobutyric Acid - biosynthesis; Heart Rate - drug effects; Hypotheses; Hypothesis testing; Inhibition; Inhibitor drugs; Lactic acid; Male; Maze Learning - physiology; Medical sciences; Muscimol; Neuropharmacology; Neurotransmitters; Nuclei; Panic; Panic attacks; Panic disorder; Pharmacology. Drug treatments; Physiologic salines; Physiological aspects; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Rodents; Septal Nuclei - metabolism; Septal Nuclei - physiopathology; Social Behavior; Sodium; Sodium lactate; Sodium Lactate - administration & dosage; Sodium Lactate - pharmacology; Stria terminalis; Tachycardia; Tachypnea; γ-Aminobutyric acid A receptors
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881107082902

The current study tested the hypothesis that chronic loss of inhibitory GABAergic tone in the bed nucleus of the stria terminalis (BNST), a region implicated in anxiety behavior, results in generalized anxiety disorder-like behaviors without panic-like responses (i.e., tachycardia, hypertension and tachypnea) following panicogenic stimuli (e.g., sodium lactate infusions). To test this hypothesis, the GABA synthesis inhibitor L-allylglycine (L-AG) or its inactive isomer D-AG was chronically infused into the BNST of male rats via osmotic mini-pumps. L-AG, but not D-AG, treated rats had increased anxiety-like behavior as measured by social interaction (SI) and elevated-plus maze paradigms. Restoring GABAergic tone, with 100pmoles/100nl of muscimol (a GABAA receptor agonist), in the BNST of L-AG treated rats attenuated L-AG-induced anxiety-like behavior in the SI test. To assess panic-like states, L-AG treated rats were intravenously infused with 0.5 M sodium lactate, a panicogenic agent, prior to assessing SI and cardiorespiratory responses. L-AG decreased SI duration again; however, sodium lactate did not induce panic-like cardiorespiratory responses. These findings demonstrate that GABA inhibition in the BNST elicits anxiety-like behavior without increasing sensitivity to lactate, thus suggesting a behavioral profile similar to that of generalized anxiety-like behavior rather than that of panic.