Behavioral reactivity to stress: amplification of stress-induced noradrenergic activation elicits a galanin-mediated anxiolytic effect in central amygdala.
Brain norepinephrine (NE) modulates many aspects of the stress response. The interaction between NE and neuropeptides such as galanin, with which it is closely associated and which may be released from noradrenergic terminals under conditions of high activity, has not been well studied. We therefore investigated the modulatory effects of galanin in the central nucleus of the amygdala (CeA) on behavioral responsivity to stress when activation of the noradrenergic system was amplified using the adrenergic autoreceptor antagonist yohimbine (2.5 mg/kg ip). Either immobilization stress or yohimbine alone had anxiogenic effects on rat behavior in the elevated plus maze. However, yohimbine pretreatment before stress produced a paradoxical anxiolytic response, which we hypothesized was attributable to galanin release in CeA. Microdialysis verified that yohimbine amplified NE release in CeA during immobilization stress, and also showed that whereas there was no detectable change in galanin release in CeA during stress alone, there was an increase during immobilization stress after yohimbine pretreatment. Bilateral administration of the galanin antagonist M40 into CeA before stress blocked the anxiolytic influence of yohimbine pretreatment. Exogenous galanin mimicked the anxiolytic effect of yohimbine pretreatment, and this too was blocked by M40. These results suggest that amplifying the noradrenergic response to stress can recruit galanin release in CeA, which buffers the anxiety-like behavioral response to acute stress. The balance between noradrenergic and peptidergic neurotransmission may be modified by prior stress, drug treatment or genetic variability, and may represent a novel target for treatment of stress-related neuropsychiatric disorders.
Khoshbouei
Habibeh
H
Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Cecchi
Marco
M
Dove
Stephanie
S
Javors
Martin
M
Morilak
David A
DA
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D019004:Galanin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D014151:Anti-Anxiety Agents; D015016:Yohimbine; D019004:Galanin; D009638:Norepinephrine