A buprenorphine-validated rat model of opioid use disorder optimized to study sex differences in vulnerability to relapse

Opioid withdrawal produces sex-specific effects on fentanyl-vs.-food choice and mesolimbic transcription

“…The present results are consistent with previous opioid escalation studies in male rats (31). However, the present results are in contrast to reports of female rodents showing greater rates of opioid escalation than males (24, 32-34) in some studies, but not all (35-37). Reasons for inconsistent sex differences in rates of opioid self-administration are not presently clear and could reflect differences in either the self-administered opioid or other experimental conditions.…”

“…Although sex differences in preclinical opioid abuse-related endpoints are well documented in non-opioid dependent subjects, less is known about opioid withdrawal affects sex differences in opioid reinforcement. Recent preclinical rodent studies suggest opioid withdrawal leads to protracted, sex-specific effects on somatic withdrawal signs, opioid self-administration, and reinstatement (e.g., (22)(23)(24)). However, sex differences in opioid-withdrawal effects on opioid-vs.-food choice are unexplored.…”

Influence of Contingent and Noncontingent Drug Histories on the Development of High Levels of MDPV Self-Administration

“…Others have also reported fairly large variability in fentanyl intake in rats whose responding was maintained by intravenous or vapor fentanyl (e.g., Stevenson et al, 2020;Bakhti-Suroosh et al, 2021;McConnell et al, 2021), suggesting that fentanyl may facilitate a high-responder phenotype similar to that seen with MDPV self-administration. Taken together with recent findings suggesting that the high-responder phenotype persists when oxycodone is substituted for MDPV (Gannon et al, 2021), the current findings highlight the need to further explore interactions between this high-responder phenotype and opioid self-administration.…”

The effects of neonatal procedural pain and maternal isolation on hippocampal cell proliferation and reelin concentration in neonatal and adult male and female rats

“…Because reelin levels vary with age (as reviewed by Doehner & Knuesel, 2010) and estrus stage in females (Meseke et al., 2018), and because Ki67 + cell density decreases with age (Bath, Manzano‐Nieves, & Goodwill, 2016), the age of all adult subjects at sacrifice was assessed as a covariate in analyses of reelin and Ki67, and estrus stage was assessed as a covariate in female‐only analyses of reelin. For statistical tests of estrus phase as a covariate, estrus phase was entered into analyses as a dummy coded variable for estrus versus nonestrus (as described previously by Bakhti‐Suroosh et al., 2021; Gaulden et al., 2021; Kerstetter et al., 2008; Peterson et al., 2014; for statistical tests that evaluated other estrus phases as dummy coded covariates, see Supplemental Data). Subjects were excluded from analyses if they were identified as extreme multivariate or univariate outliers for Ki67 + cell density or reelin SAF.…”

“…Females were lavaged before each day of testing to determine their estrus phase via cytology of cresyl violet stained lavage slides(Mooney-Leber & Brummelte, 2020). Estrus phase was encoded as either metestrus, diestrus, proestrus, or estrus(Heykants & Mahabir, 2016;Marcondes, Bianchi, & Tanno, 2002;Paccola, Resende, Stumpp, Miraglia, & Cipriano, 2013;Westwood, 2008) and then further grouped together as estrus versus nonestrus (nonestrus including metestrus, diestrus, and proestrus, as described previously byBakhti-Suroosh, Towers, & Lynch, 2021;Gaulden et al, 2021;Kerstetter, Aguilar, Parrish, & Kippin, 2008;Peterson, Hivick, & Lynch, 2014).…”