Pharmacokinetics of Injectable Meloxicam and Buprenorphine in the Naked Mole-Rat (Heterocephalus glaber).

Unique characteristics of the naked mole-rat (NMR) have made it increasingly popular as a laboratory animal model. These rodents are used to study many fields of research including longevity and aging, cancer, circadian rhythm, pain, and metabolism. Currently, the analgesic dosing regimens used in the NMR mirror those used in other rodent species. However, there is no pharmacokinetic (PK) data supporting the use of injectable analgesics in the NMR. Therefore, we conducted 2 independent PK studies to evaluate 2 commonly used analgesics in the NMR: meloxicam (2 mg/kg SC) and buprenorphine (0.1 mg/kg SC). In each study, blood was collected at 8 time points after subcutaneous injection of meloxicam or buprenorphine (0 [predose], 0.25, 0.5, 1, 2, 4, 8, and 24 h). Three NMRs were used per time point for a total of 24 animals per PK study. Plasma concentrations of meloxicam were highest between 0.5 and 1 h postinjection. Levels remained above the extrapolated dog and cat therapeutic threshold levels (390 to 911 ng/mL) for at least 24 h. Plasma concentrations of buprenorphine were highest between 0.25 and 0.5 h postinjection. Levels remained above the human therapeutic threshold (1 ng/mL) for up to 21 h. No skin reactions were seen in association with injection of either drug. In summary, these data support dosing meloxicam (2 mg/kg SC) once every 24 h and buprenorphine (0.1 mg/kg SC) once every 8 to 12 h in the NMR. Further studies should be performed to evaluate the clinical efficacy of these drugs by correlating plasma concentrations with postoperative pain assessments.

The role of the estrogen receptor-α gene, Esr1, in maternal-like behavior in juvenile female and male rats.

The estrogen receptor-alpha (ER-α) is an important ligand activated transcription factor that works to control gene transcription in many species. Previous studies have shown estrogen to be an important hormone in the regulation of maternal behavior. Like adult female rats, both male and female juvenile rats exhibit increased level of maternal-like behavior when exposed to pups. The aim of this study was to determine whether ER-α is critical for the expression of maternal-like behavior in juvenile male and female rats. ER-α knock-out and wildtype (WT) juvenile male and female rats were generated and tested for maternal behaviors. Latencies to display maternal-like behaviors that included retrieval, grouping and crouching responses, revealed no genotype differences between KO and WT subjects. Male juvenile rats exhibited slightly shorter latencies than WT juvenile female rats indicating a sex difference in the latency to display these responses. Additionally, ER-α KO females exhibited a delay in onset of vaginal opening compared to WT females, indicating a role for ER-α in sexual maturation. The behavioral findings indicate that ER-α is not obligatory for the expression of full maternal-like behavior in male and female juvenile rats. Understanding this neurobiological system will help to elucidate the developmental involvement of the endocrine and brain networks in the regulation of maternal behaviors in mammals.