Oprk1-KO Mouse

OPRK1, short for opioid receptor kappa 1, encodes the κ-opioid receptor which is a member of the opioid family. This receptor plays crucial roles in multiple physiological functions such as cognitive and learning processes. It is also involved in the regulation of the gonadotropin-releasing hormone (GnRH) pulse and surge through its expression in kisspeptin neurons, which impacts the estrous cycle and fertility in female rats [2]. The dynorphin (DYN)/Kappa Opioid Receptor (KOR) system, where OPRK1 is a key component, has been suggested to be associated with negative affective states and alcohol-related behaviors [3].

In a study using Kiss1-floxed/Oprk1-Cre rats (a conditional knockout model), deletion of Kiss1 in Oprk1-expressing kisspeptin neurons led to estrogen-dependent LH pulse disruption and LH surge attenuation in female rats. This indicates that Oprk1-expressing kisspeptin neurons in the arcuate and AVPV regions are essential for maintaining normal GnRH pulse and surge generation, estrous cycle length, and offspring number [2]. Regarding human studies, certain polymorphisms of OPRK1 have been associated with opioid use disorder, alcohol use disorder, and related phenotypes. For example, OPRK1 rs6473797 was associated with the risk of alcohol use disorder, and rs963549 was related to decreased opioid withdrawal and different intensities of depressive symptoms [1,3].

In conclusion, OPRK1 is essential for normal reproductive function in female rats as demonstrated by conditional knockout models. In humans, its polymorphisms are associated with substance-use disorders and related phenotypes. Research on OPRK1, especially through genetic models, helps in understanding its role in specific biological processes and disease conditions, potentially providing insights for new treatment strategies for these disorders.

References:

1. Özkan-Kotiloğlu, Selin, Kaya-Akyüzlü, Dilek, Yalçın-Şahiner, Şafak, Ayaz, Nagihan. 2023. Association of OPRK1 rs963549 and rs997917 polymorphisms with opioid use disorder and related phenotypes. In Pharmacogenomics, 24, 325-334. doi:10.2217/pgs-2023-0037. https://pubmed.ncbi.nlm.nih.gov/37166316/

2. Nagae, Mayuko, Yamada, Koki, Enomoto, Yuki, Tsukamura, Hiroko, Uenoyama, Yoshihisa. 2023. Conditional Oprk1-dependent Kiss1 deletion in kisspeptin neurons caused estrogen-dependent LH pulse disruption and LH surge attenuation in female rats. In Scientific reports, 13, 20495. doi:10.1038/s41598-023-47222-5. https://pubmed.ncbi.nlm.nih.gov/37993510/

3. Özkan-Kotiloğlu, Selin, Kaya-Akyüzlü, Dilek, Yurdakul, Rabia, Yıldırım, Mukaddes Asena, Özgür-İlhan, İnci. . Effect of PDYN and OPRK1 polymorphisms on the risk of alcohol use disorder and the intensity of depressive symptoms. In Alcohol and alcoholism (Oxford, Oxfordshire), 58, 404-414. doi:10.1093/alcalc/agad036. https://pubmed.ncbi.nlm.nih.gov/37177778/