A cre driver line for genetic targeting of kappa opioid receptor expressing cells.

Here we describe the generation and characterization of a knockin mouse line which harbors a Cre insertion in the 3'UTR of the kappa opioid receptor gene locus and provides genetic access to populations of kappa 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 mice. Chemogenetic activation of KOR-expressing cells in the basolateral amygdala (BLA 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 mice. Activation of BLA cells also attenuated KOR-agonist induced conditioned place aversion (CPA) in male mice. Overall, these results suggest a potential role for BLA cells in regulating anxiety-like behaviors and KOR-agonist mediated CPA. In summary, these results provide evidence for the utility of the newly generated mice in assessing localization, anatomy, and function of KOR circuits throughout the brain.Here we report the generation and characterization of a mouse line that harbors Cre insertion in the 3'UTR of the locus. There is high fidelity of Cre expression to KOR expressing cells throughout the brain in this mouse line and Cre insertion does not impair KOR function. Chemogenettic activation of BLA led to sex-specific effects on anxiety-like behaviors and attenuated KOR-agonist induced conditioned place aversion (CPA). These results provide evidence for the utility of the newly generated mice to interrogate KOR function in discreet circuits.