A role for the neuropeptide galanin in the neuroprotective and neuromodulatory effects of physical activity
Groves-Chapman, Jessica Lee
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Galanin expression has been shown to be upregulated in rats given free access to running wheels for three weeks. Upregulation of galanin and activation of specific galanin receptor subtypes have been linked to neuroprotection and enhanced cognitive functions. The signaling pathways through which these effects are mediated remain unknown. The first series of experiments were designed to elucidate the galanin receptor subtypes involved in neuroprotection, utilizing an intracerebroventricular (ICV) kainic acid excitotoxicity model in conjunction with receptor specific agonists. The results from these experiments indicate that the galanin receptor GALR1, and not GALR2, is required for the decrease in cell death within the Cornu Ammonis region 3 (CA3) of the hippocampus. However, none of the GALR agonists were observed to reduce seizure behavior. The purpose of the second series of experiments was to evaluate the endogenous upregulation of galanin within the locus coeruleus (LC) using an exercise model, and how this might influence behavior in a cocaine-primed condition place preference (CPP) model. The results indicate that physical activity influences cocaine-primed and stress-primed reinstatement to drug addiction in different ways. Access to a running wheel enhanced reinstatement to the drug-paired chamber following a cocaine priming injection, while reducing reinstatement to the drug-paired chamber following uncontrollable footshock. In situ hybridization analysis revealed elevated levels of galanin mRNA expression in activity animals compared to sedentary counterparts for the stress-primed reinstatement test. Additionally, it was observed that sedentary animals in the cocaine-primed reinstatement test had elevated levels of cFos mRNA expression in cortical areas compared to activity animals.