Effects of galanin on monoaminergic systems and HPA axis: Potential mechanisms underlying the effects of galanin on addiction- and stress-related behaviors

Abstract

Like a number of neuropeptides, galanin can alter neural activity in brain areas that are important for both stress-related behaviors and responses to drugs of abuse. Accordingly, drugs that target galanin receptors can alter behavioral responses to drugs of abuse and can modulate stress-related behaviors. Stress and drug-related behaviors are interrelated: stress can promote drug-seeking, and drug exposure and withdrawal can increase activity in brain circuits involved in the stress response. We review here what is known about the ability of galanin and galanin receptors to alter neuronal activity, and we discuss potential mechanisms that may underlie the effects of galanin on behaviors involved in responses to stress and addictive drugs. Understanding the mechanisms underlying galanin's effects on neuronal function in brain regions related to stress and addiction may be useful in developing novel therapeutics for the treatment of stress- and addiction-related disorders.

Figure 1. Schematic representation of potential pathways involved in the actions of galanin on brain regions involved in drug reward, behavioral responses to stress and opiate withdrawal

Noradrenergic neurons of the LC co-express galanin and send projections to the VTA, the PVN and the SON (Grenoff et al 1993; Levin et al., 1987). The PVN sends -opioid and CRF projections to the VTA (Quinn et al., 2003; Rodaros et al., 2007), which project dopaminergic fibers to the NAc. Numerous studies have shown that galanin can alter neuronal activity in the dopaminergic system, the LC and the HPA axis. Local infusions of galanin modulate striatal acetylcholine release (Ögren, et al., 1993; Antoniou, et al., 1997). Moreover, central administration of galanin decreases dopamine release in the striatum, likely through a GalR1-mediated mechanism (Tsuda et al., 1998; Ericson and Ahlenius, 1999; Counts et al., 2002). In contrast, galanin injected into the PVN increases dopamine release in the NAc (Rada et al., 1998). The PVN is the primary location of CRF-positive neurons and is a key site for the HPA axis response to stress leading to increased adrenocorticotropic hormone (ACTH) release in the anterior pituitary. The action of galanin on the HPA axis under stressful conditions is inhibitory. Evidence suggests that GalR1 receptors in the LC inhibit noradrenaline release in the PVN, which in turn reduces exacerbated activity of the HPA axis. VTA, ventral tegmental area; SN, subtantia nigra; NAc, nucleus accumbens; PVN, paraventricular nucleus; TH, tyrosine hydroxylase; ACh, acetylcholine; NE, norepinephrin; 5-HT, serotonin; AVP, arginin vasopressin; CRF, corticotropin-releasing factor; ACTH, adrenocorticotropic hormone.