Effects of acute and repeated restraint stress on gaba efflux in the rat basolateral and central amygdala

Abstract

Stress can precipitate onset of multiple mood-related disorders, including depression. Examination of the neural basis of this phenomenon has highlighted the amygdala as a key component. Alterations in amygdalar activity and structure accompany various mood-related disorders, and interestingly, amygdalar morphology and behavior can be altered in animals subjected to repeated stress. Gamma-aminobutyric acid (GABA) transmission in the amygdala represents an important means by which information flow, activity, and function can be controlled; therefore, we determined the effects of acute and repeated restraint stress (RRS) on GABA efflux in the basolateral and central amygdalar complexes. In vivo microdialysis revealed that acute restraint stress increased GABA efflux in the basolateral amygdala, whereas central amygdala efflux remained unchanged. Animals subjected to prior repeated stress displayed no acute stress-mediated increases in GABA efflux in the basolateral amygdala, an event accompanied by no changes in basal GABA concentrations. Conversely, repeated restraint stress had no effect on GABA efflux or basal GABA levels in the CeA. Collectively, these data demonstrate that acute stress elicits unique and region-specific increases in GABA efflux in the rat amygdala, and that prior repeated stress differentially modifies this response.

Introduction

Stress has been associated with onset or precipitation of mood-related disorders (Gold et al., 1988, Gold et al., 1988, Sheline, 2000). Elucidation of the neural substrates important for this association has highlighted the amygdala as key component. The amygdala is integral for the regulation of emotional behaviors (LeDoux, 2000), as well as the coordination of stress responses, as indicated by anatomical (Cullinan et al., 1995), neurochemical (Cook, 2004), behavioral (Muller et al., 2003) and physiological studies (Maroun and Richter-Levin, 2003). Alterations in amygdalar activity (Thomas et al., 2001, Hull, 2002, Drevets, 1999) and structure (Frodl et al., 2002); (Brambilla et al., 2003) accompany various mood-related disorders and interestingly, amygdalar morphology and behavior can be modulated in animal models subjected to repeated stress (McEwen and Chattarji, 2004, Mitra et al., 2005, Vyas et al., 2002).

Gamma-aminobutyric acid (GABA) transmission in the amygdala represents an important means by which information flow, activity, and function can be controlled (Cassell et al., 1999, Davis et al., 1994, Woodruff et al., 2006). For example, GABA transmission in the basolateral amygdalar complex (BLC) is postulated to modulate memory storage (Castellano et al., 1989), as well as acquisition of conditioned fear (Wilensky et al., 2000, Holahan and White, 2004, Holahan and White, 2004). Similarly, GABA transmission in the central amygdala (CeA) is also important for modulating function and activity. Unlike the BLC, however, the role GABA plays in modulating CeA function is less lucid. For example, electrophysiological data indicate that depending upon the type of receptor targeted, GABA agonists can either potentiate or block inhibitory responses in the CeA (Delaney and Sah, 1999). Thus, knowing the overall importance of GABA transmission in the amygdala, we set out to determine the effects of acute restraint stress (RS) on GABA efflux in the rat BLC and CeA. Further, to gain insight into more pathologically-relevant conditions, we set out to determine the effects of repeated RS on GABA efflux in these nuclei.