Effects of galanin on striatal excitation and morphone conditioned place preference

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 post-synaptic potentials (EPSPs) using both field and whole-cell recordings from striatal brain slices extracted from wild type mice and mice lacking specific galanin receptor (GaIR) subtypes. We found that galanin and the non-peptide galanin receptor agonist galnon decrease the amplitude of EPSPs in both the dorsal striatum and nucleus accumbens (NAc), and that an oppositional effect of galanin and morphine cannot be identified with this method. We then performed recordings in slices from knockout mice lacking either the Ga1R1 or Ga1R2 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 GaIR1 and Ga1R2 mice for morphine conditioned place preference (CPP). Morphine CPP was significantly attenuated in both GalR1 and Ga1R2 knockout mice. We also infused galanin into the NAc to test whether this brain region mediates the ability of galanin infused into the ventricle to attenuate morphine CPP, and found the NAc galanin infusion does not change morphine CPP. Together, these data suggest that mesolimbic excitatory signaling is significantly modulated by galanin in a GaIR1- and Ga1R2-dependent manner and that morphine CPP is dependent on the same receptor subtypes.