A Cre Driver Line for Genetic Targeting of Kappa Opioid Receptor Expressing Cells.

Here we describe the generation and characterization of a Cre knock-in mouse line that harbors a Cre insertion in the 3'UTR of the k opioid receptor gene (Oprk1) locus and provides genetic access to populations of k opioid receptor (KOR)-expressing neurons throughout the brain. Using a combination of techniques including RNA in situ hybridization and immunohistochemistry, we report that Cre is expressed with high fidelity in KORexpressing cells throughout the brain in this mouse line. We also provide evidence that Cre insertion does not alter basal KOR function. Baseline anxiety-like behaviors and nociceptive thresholds are unaltered in Oprk1-Cre mice. Chemogenetic activation of KOR-expressing cells in the basolateral amygdala (BLAKOR cells) resulted in several sex-specific effects on anxiety-like and aversive behaviors. Activation led to decreased anxiety-like behavior on the elevated plus maze and increased sociability in female but not in male Oprk1-Cre mice. Activation of BLAKOR cells also attenuated KOR agonist-induced conditioned place aversion (CPA) in male Oprk1-Cre mice. Overall, these results suggest a potential role for BLAKOR cells in regulating anxiety-like behaviors and KOR-agonist mediated CPA. In summary, these results provide evidence for the utility of the newly generated Oprk1-Cre mice in assessing localization, anatomy, and function of KOR circuits throughout the brain.