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

Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

^* To whom correspondence should be addressed.

	Abstract

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.

Key Words: amygdala, elevated–plus maze, fear, anxiety disorder, muscimol, panic, BNST, stria terminalis, social interaction

First published on February 28, 2008, doi:10.1177/0269881107082902

Journal of Psychopharmacology 2008;22:633.

A more recent version of this article appeared on August 1, 2008


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