The neuropeptide galanin has been shown to modulate opiate dependence and withdrawal. These effects could be mediated via activation of one or more of three distinct G-protein coupled receptors, namely GalR1, GalR2 and GalR3.
In this study, we used several transgenic mouse lines to further define the mechanisms underlying the role played by galanin and its receptors in the modulation of morphine dependence. Firstly, transgenic mice expressing β-galactosidase under the control of the galanin promoter were used to assess the regulation of galanin expression in response to chronic morphine administration and withdrawal. Next, the behavioural responses to chronic morphine administration and withdrawal were tested in mice that over-express galanin, lack the GalR1 gene or lack the GalR2 gene.
Transgenic and matched wild-type mice were given increasing doses of morphine followed by precipitation of withdrawal by naloxone and behavioral responses to withdrawal assessed.
Both morphine administration and withdrawal increases galanin gene transcription in the locus coerulus (LC). Increasing galanin levels in the brain reduced signs of opiate withdrawal. Mice lacking GalR1 undergo more severe opiate withdrawal, whereas mice lacking GalR2 show no significant difference in withdrawal signs, compare to matched wild type controls.
Opiate administration and withdrawal increase galanin expression in the LC. Galanin opposes the actions of morphine which lead to opiate dependence and withdrawal, an effect that is mediated via GalR1.