PT - JOURNAL ARTICLE AU - Paliarin, Franciely AU - Duplantis, Chelsea AU - Jones, Andrea F. AU - Cucinello-Ragland, Jessica AU - Basavanhalli, Samhita AU - Blaze, Emily AU - Doré, Evan AU - Neel, Anna Isabella AU - Sun, Haiguo AU - Chen, Rong AU - Edwards, Scott AU - Gilpin, Nicholas W. AU - Messing, Robert O. AU - Maiya, Rajani TI - A Cre Driver Line for Genetic Targeting of Kappa Opioid Receptor Expressing Cells AID - 10.1523/ENEURO.0043-23.2023 DP - 2023 Jul 01 TA - eneuro PG - ENEURO.0043-23.2023 VI - 10 IP - 7 4099 - http://www.eneuro.org/content/10/7/ENEURO.0043-23.2023.short 4100 - http://www.eneuro.org/content/10/7/ENEURO.0043-23.2023.full SO - eNeuro2023 Jul 01; 10 AB - 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 κ opioid receptor gene (Oprk1) locus and provides genetic access to populations of κ 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 KOR-expressing 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.