Characterization of a rat model expressing Cre recombinase in oxytocinergic neurons: NTac:SD-Oxtem1(cre)Sage

Abstract

Oxytocin is a nonapeptide synthesized and released in both the central nervous system and periphery involved in numerous physiological and neurological processes. These include parturition and lactation, blood pressure regulation, social bonding, anxiety, substance use disorders, and nociception among others. Several animal models have been used to study the oxytocinergic system mechanistically, including prairie voles, mice, and rats, and genetically modified strains exist for these species. Here we describe the generation and characterization of a transgenic rat that expresses Cre recombinase in oxytocinergic neurons. Rats were generated on a Sprague-Dawley background using CRISPR and verified for the Cre recombinase gene downstream of the gene encoding oxytocin separated by a P2A sequence. Levels of mRNA for oxytocin, vasopressin, and oxytocin and vasopressin1a receptors were found to be no different between genotypes in brain and spinal cord. Oxytocin was found to be marginally decreased in the PVN and SON of Cre+ compared to wild-type littermates, with vasopressin marginally increased in spinal cord of female Cre+ rats compared to wild-type. Functional Cre expression was verified in brain using viral transfection of floxed reporter genes and using an ablative strategy by viral delivery of a floxed mutated caspase. Offspring were assessed for weight growth and a variety of behaviors, including exploratory activity, attention and impulsivity, and opioid reinforcement. Weight gain and all behaviors were similar between transgenic and wild-type littermates. These animals should prove to be a valuable resource for exploring oxytocin’s role in physiology and behavior.