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 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.

D2 receptor antagonism enhances cocaine-induced behavioral sensitization in female, but not male Japanese quail ( Coturnix japonica ).

Sex differences in cocaine-induced behaviors are well established. In rodents, females show enhanced locomotion to cocaine over multiple trials compared with males, a behavioral response known as sensitization. Estradiol enhances cocaine-induced sensitization in female rats by agonizing dopaminergic activity within the brain. In female quail, cocaine does not increase locomotion regardless of increased estradiol. A higher D2:D1 dopamine receptor ratio in quail compared with rodents may explain this sex and species difference. The goal of the present work was to investigate the role of D2 receptors in cocaine-induced locomotion and sensitization in Japanese quail and to determine whether a greater D2 receptor availability contributed to the lack of cocaine-induced sensitization in female quail found in previous studies. Male and female quail were administered 0, 0.03, 0.05, or 0.07 mg/kg of eticlopride (Eti) followed by 10 mg/kg of cocaine or saline then immediately placed in open-field chambers. Distance traveled was recorded for 30 min daily for 7 days. In female quail, cocaine-induced sensitization was observed with 0.03 or 0.05 mg/kg Eti, but not in cocaine-only females. In male quail, cocaine-induced sensitization was observed similar to previous research. However, Eti did not enhance cocaine-induced locomotion or produce sensitization in male quail. The D2 receptor likely mediates cocaine's motor stimulating effects in quail. In females, this effect is more pronounced. Since high D2 availability is protective against stimulant abuse, Japanese quail may be a useful model for investigating the role of the D2 receptor in cocaine addiction, but further research is needed.