Behavioral and genetic markers of susceptibility to escalate fentanyl intake.

Background: The "loss of control" over drug consumption, present in opioid use disorder (OUD) and known as escalation of intake, is well-established in preclinical rodent models. However, little is known about how antecedent behavioral characteristics, such as valuation of hedonic reinforcers prior to drug use, may impact the trajectory of fentanyl intake over time. Moreover, it is unclear if distinct escalation phenotypes may be driven by genetic markers predictive of OUD susceptibility.

Effects of isolation stress and voluntary ethanol exposure during adolescence on ethanol and nicotine co-use in adulthood using male rats.

Background: Alcohol use in adolescence may increase susceptibility to substance use disorders (SUDs) in adulthood. This study determined if voluntary ethanol (EtOH) consumption during adolescence, combined with social isolation, alters the trajectory of EtOH and nicotine intake during adulthood, as well as activating brain neuroinflammation.

Methods: Adolescent male isolate- and group-housed rats were given 0.

On the Addams family of discrete frailty distributions for modeling multivariate case I interval-censored data.

Random effect models for time-to-event data, also known as frailty models, provide a conceptually appealing way of quantifying association between survival times and of representing heterogeneities resulting from factors which may be difficult or impossible to measure. In the literature, the random effect is usually assumed to have a continuous distribution. However, in some areas of application, discrete frailty distributions may be more appropriate.

Targeting α- and α-adrenergic receptors as a countermeasure for fentanyl-induced locomotor and ventilatory depression.

This study assessed the ability of α and α-adrenergic drugs to decrease fentanyl-induced locomotor and ventilatory depression. Rats were given saline or fentanyl, followed by: (1) naltrexone, (2) naloxone, (3) nalmefene, (4) α agonist phenylephrine, (5) α antagonist prazosin, (6) α antagonist BMY-7378, (7) α agonist clonidine, (8) α antagonist yohimbine or (9) vehicle. All µ-opioid antagonists dose-dependently reversed fentanyl-induced locomotor and ventilatory depression.