Infusion of growth hormone into the hippocampus induces molecular and behavioral responses in mice

Growth hormone (GH) has been implicated in a variety of brain functions, including neural development, cognition, and neuroprotection. The biological effects of GH are known to rely on the binding of GH to the GH receptor (GHR), yet the resulting signals in the brain remain poorly understood. The present study investigated the effects of hippocampal infusions of recombinant GH and a GHR antagonist on the expression of immediate early genes (IEGs) and behavioral responses in mice. The infusions induced differential expression of Arc, Nr4a1, and Npas4 mRNAs among the IEGs. The infusions also elicited differential behavioral responses, such as varied levels of spontaneous locomotion, self-grooming, and frequency of access to the corner fields in the open-field test. Polynomial regression analyses and canonical discriminant analyses between gene expression and behavioral changes demonstrated that the expression level of Arc mRNA was strongly correlated with locomotor activity level (r = 0.71 and 0.92 on days 8 and 10, respectively) and that the correlation was completely discriminable between drugs (error rate = 0%). This analysis also revealed that a decrease in Npas4 mRNA was negatively correlated with the number of corner accesses (r = -0.63) and that this correlation was partially discriminable between drugs (error rate = 16.67%). Taken together, these results suggest that the GH-GHR complex modulates Arc and Npas4 signaling, which affects spontaneous locomotor and exploratory behaviors.