Modulatory Effects of Galanin in the Lateral Bed Nucleus of the Stria Terminalis on Behavioral and Neuroendocrine Responses to Acute Stress

Abstract

The neuropeptide galanin has been identified as a possible neurotransmitter/neuromodulator within the central nervous system. In the present study, a potential role for galanin in the lateral bed nucleus of the stria terminalis (BSTL) in modulating behavioral and neuroendocrine responses to an acute stress was investigated. In the first experiment, acute immobilization stress induced anxietylike behavioral responses in ratsSince its discovery (Tatemoto et al. 1983), the peptide neurotransmitter galanin has been implicated in numerous autonomic and physiologic regulatory processes, including feeding (Crawley 1999), cardiovascular control (Shih et al. 1996), learning and memory (McDonald et al. 1998), and the response to stress (Holmes et al. 1995; Khoshbouei et al. 2000;Sweerts et al. 1999Sweerts et al. , 2000. Furthermore, it has been hypothesized that galanin may also be involved in disease states such as depression (Seutin et al. 1989), feeding disorders (Crawley et al. 1990(Crawley et al. , 1993, and Alzheimer's disease (Bartfai et al. 1992;Mufson et al. 1993Mufson et al. , 1998Mufson et al. , 2000.Limbic forebrain structures important for the expression of fear and anxiety, such as the central nucleus of the amygdala and the bed nucleus of the stria terminalis (BST), show a rich expression of galanin and galanin receptors (Bartfai et al. 1992; Gustafson et al. 1996; Melander et al. 1986a,b). Within the BST, there is extensive overlap between galanin-immunoreactive terminals and galanin receptors (Gray and Magnuson 1987b; . 1993b, 1997). The BST is a component of the "extended amygdala", which plays a critical role in the integration of autonomic and behavioral responses to stress (Davis and Shi 1999; Davis et al. 1997a; Herman and Cullinan 1997). The lateral BST (BSTL) in particular has been implicated in modulation of behavioral-affective responses (Cecchi et al. 2001; Davis and Shi 1999). Lesions of the BST blocked the enhancement of acoustic startle induced by i.c.v. infusion of CRH (Davis et al. 1997b). Similarly, blockade of glutamate receptors in BSTL antagonized the unconditioned potentiation of startle induced by exposure to bright light (reviewed by (Davis and Shi 1999)).In addition to playing a potential role in modulating the behavioral response to stress, the BSTL also exerts an extrahypothalamic modulatory influence on stressinduced hypothalamic-pituitary-adrenal (HPA) activation (Cecchi et al. 2001; Herman and Cullinan 1997; Herman et al. 1996). While some investigators have suggested that the BST has an inhibitory influence on HPA activation (Herman and Cullinan 1997), others have suggested a facilitatory role. A small cluster of CRF-immunoreactive neurons in ventrolateral BST project to mid-parvocellular PVN (Moga and Saper 1994). Lesions of BST attenuated the increase in plasma ACTH and corticosterone induced by reintroduction of rats into a context in which they had previously been exposed to foot shock (Gray et al. 1993), and specific lesioning of anterolateral BST cause a decrease ...

GAL 3 receptor KO mice exhibit an anxiety-like phenotype

“…Anxiogenic-like actions of GAL were induced in the punished drinking test following microinjections of the peptide into the rat amygdala (27). Furthermore, whereas administration of the GAL antagonist M40 into the lateral BNST had no effect on the baseline behavior of rats, M40 attenuated the anxiogenic-like effects of immobilization stress, suggesting that endogenous GAL released in the lateral BNST facilitates acute behavioral reactivity to stress (28). Furthermore, the release of GAL in the central amygdala was increased when the noradrenergic response to stress was amplified by administration of the α2-adrenoreceptor antagonist yohimbine.…”

Galanin GAL-R1 Receptor Null Mutant Mice Display Increased Anxiety-Like Behavior Specific to the Elevated Plus-Maze

“…Khoshbouei et al (2002b) found that both anxietylike (elevated plus-maze, social interaction tests) and neuroendocrine (plasma adrenocorticotropin) responses to acute restraint stress in rats were blocked by administration of the nonspecific galanin receptor antagonist, M40, directly into the bed nucleus of the stria terminalis. In a separate study, Khoshbouei et al (2002a) found that rats subject to the combined stress of restraint and treatment with yohimbine, an a2 adrenergic autoreceptor antagonist that increases norepinephrine release in limbic regions, displayed a paradoxical decrease in anxiety-like behavior on the elevated plus-maze, as compared to either stressor alone.…”

Gender-Specific Association of Galanin Polymorphisms with HPA-Axis Dysregulation, Symptom Severity, and Antidepressant Treatment Response

“…It has been hypothesized that GAL affects stress-related behavior by interacting not only with monoaminergic neurotransmitters such as serotonin (5-HT) and noradrenaline, but also with g-aminobutyric acid (Fuxe et al, 1998;Kehr et al, 2002;Khoshbouei et al, 2002a;Ma et al, 2001;Sharkey et al, 2008;Tyszkiewicz et al, 2008;Xu et al, 1998). GAL expression in the LC and limbic nuclei may be stimulated by stress (Holmes et al, 1995;O'Neal et al, 2001;Sweerts et al, 1999) and seems to have a significant impact on hypothalamic-pituitary-adrenal (HPA)-axis signaling (Brogan et al, 1999;Khoshbouei et al, 2002b;Lopez et al, 1991;Malendowicz et al, 1994). In preclinical and clinical studies, corticotropin-releasing hormone (CRH) and vasopressin (AVP) have been shown to be the main effectors of HPA activity, important for the mediation of anxious and depressive-like behavior (Britton et al, 1986;Holsboer, 2000;Landgraf, 2006;Nemeroff and Owens, 2002;Pepin et al, 1992;Stenzel-Poore et al, 1994;Strohle et al, 1998).…”