Galanin-induced decreases in nucleus accumbens/striatum excitatory postsynaptic potentials and morphine conditioned place preference require both galanin receptor 1 and galanin receptor 2

Abstract

The neuropeptide galanin has been shown to alter the rewarding properties of morphine. To identify potential cellular mechanisms that might be involved in the ability of galanin to modulate opiate reward, we measured excitatory postsynaptic potentials (EPSPs), using both field and whole-cell recordings from striatal brain slices extracted from wild-type mice and mice lacking specific galanin receptor (GalR) subtypes. We found that galanin decreased the amplitude of EPSPs in both the dorsal striatum and nucleus accumbens. We then performed recordings in slices from knockout mice lacking either the GalR1 or GalR2 gene, and found that the ability of galanin to decrease EPSP amplitude was absent from both mouse lines, suggesting that both receptor subtypes are required for this effect. In order to determine whether behavioral responses to opiates were dependent on the same receptor subtypes, we tested GalR1 and GalR2 knockout mice for morphine conditioned place preference (CPP). Morphine CPP was significantly attenuated in both GalR1 and GalR2 knockout mice. These data suggest that mesolimbic excitatory signaling is significantly modulated by galanin in a GalR1-dependent and GalR2-dependent manner, and that morphine CPP is dependent on the same receptor subtypes. Galanin modulates morphine's behavioral effects in mice. This study identifies direct actions on excitation of striatal neurons and identifies the galanin receptor (GalR) subtypes involved. Galanin decreases the amplitude of excitatory postsynaptic potentials in medium spiny neurons of wild type mice, but not mice lacking the GalR1 or GalR2 subtype. Neither GalR1 nor GalR2 knockout mice exhibit conditioned place preference for morphine. Thus both phenotypes depend on GalR1 and GalR2. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.