Galanin-mediated anxiolytic effect in rat central amygdala is not a result of corelease from noradrenergic terminals

Abstract

Galanin is colocalized extensively with norepinephrine in brain. Although this suggests possible activity-dependent neurotransmitter interactions, the functional significance of such colocalization remains elusive. Previously, we showed that enhancing stress-activation of the noradrenergic system by yohimbine pretreatment released galanin in central amygdala, attenuating the anxiety-like behavioral response to stress on the elevated plus-maze. The present study was conducted to determine, in this context, whether galanin was indeed coreleased from noradrenergic terminals, or instead from another galanin afferent or local stress-responsive galanin neurons in the amygdala. In experiment 1, galanin-mediated anxiolytic effects on the plus-maze following yohimbine + stress were unaltered by lesioning the noradrenergic innervation of central amygdala. In experiment 2, combining immunohistochemistry and in situ hybridization, galanin neurons specifically activated by yohimbine + stress treatment were found only in the locus coeruleus and intraamygdalar bed nucleus of the stria terminalis, adjacent to central amygdala. In experiment 3, retrograde tracing combined with in situ hybridization revealed few if any galanin cells projecting to central amygdala in locus coeruleus or nucleus tractus solitarius, sources of noradrenergic innervation. Indeed, few retrogradely-labeled galanin neurons were observed anywhere in the brain, including a small number in the intraamygdalar bed nucleus. Together, these results suggest that stress following yohimbine may have induced galanin release from an afferent to central amygdala originating in the bed nucleus, or from local neurons in the intraamygdalar bed nucleus, but that anxiolytic effects exerted by galanin in this context of elevated noradrenergic activity were not the result of corelease from noradrenergic terminals innervating central amygdala.

Complex Biphasic Changes of Neuropeptide Concentrations in the Rat Limbic System During Pregnancy and Parturition~!2009-10-10~!2010-03-14~!2010-06-25~!

“…This peptide, present in both dorsal raphe and locus coeruleus projecting to the frontal cortex and hippocampus has been implicated in both stress-related behavior as well as anxiety [22] e.g. from studies of the bed nucleus of stria terminalis located immediate adjacent to the central nucleus of amygdala [42]. On the contrary, we found that CCK-LI concentration was reduced in the frontal cortex postpartum by 26%.…”

Bidirectional regulation of stress responses by galanin in mice: Involvement of galanin receptor subtype 1

“…There are many conflicting reports of the role of galanin in stress-related behavioral phenotypes, such as anxiogenic-like (Moller et al, 1999, Khoshbouei et al, 2002b, Echevarria et al, 2005, Swanson et al, 2005), anxiolytic-like (Bing et al, 1993, Holmes et al, 2002, Khoshbouei et al, 2002a, Barrera et al, 2006) or no effects (Karlsson et al, 2005, Kuteeva et al, 2005). The role of galanin in stress-related behaviors seems to be complex depending on the animal species, route and site of drug administration and behavioral paradigms employed (Lu et al, 2005b, Karlsson and Holmes, 2006, Rajarao et al, 2007), reflecting the complex galaninergic innervation in the CNS and the discrete yet partially overlapping patterns of the three galanin receptor subtypes (GalR1 – 3).…”

Neuropeptide modulation of central amygdala neuroplasticity is a key mediator of alcohol dependence

“…High levels of Gal1, Gal2 and Gal3 receptors are expressed in amygdala (Branchek et al, 2000; Waters et al, 2000). Galanin administered into the ventricles is anxiolytic (Bing et al, 1993) and galanin infused directly into CeA reduces stress-induced anxiety (Khoshbouei et al, 2002; Barrera et al, 2006; but see Moller et al, 1999). Stressful stimuli release galanin (Weiss et al, 2005) and increase galanin mRNA in CeA (Palkovits et al, 2000).…”