Sub-chronic nicotine exposure influences methamphetamine self-administration and dopamine overflow in a sex-and genotype-dependent manner in humanized 6 3'-UTR SNP (rs2304297) adolescent rats.

The rewarding effects of drugs of abuse are associated with the dopaminergic system in the limbic circuitry. Nicotine exposure during adolescence is linked to increased use of drugs of abuse with nicotine and methamphetamine (METH) commonly used together. Nicotine acts on neuronal nicotinic acetylcholine receptor (nAChR) systems, critical for reward processing and drug reinforcement, while METH leads to a higher dopamine (DA) efflux in brain reward regions.

Impact of tobacco smoke constituents on nicotine-seeking behavior in adolescent and adult male rats.

Introduction: Given the rapid increase in teen vaping over recent years it is critical to understand mechanisms underlying addiction and relapse to tobacco use at this age. To evaluate the role of non-nicotine constituents in cigarette smoke, our lab has previously established a model of intravenous self-administration of aqueous cigarette smoke extract (CSE). We now compare the sensitivity of male adolescent and adult rats who have self-administered CSE or nicotine to reinstatement with the pharmacological stressor, yohimbine, with and without cues.

Sex- and genotype-dependent nicotine plus cue-primed reinstatement is enhanced in adolescent Sprague Dawley rats containing the human 6 3'-UTR polymorphism (rs2304297).

Rationale: Large-scale human candidate gene studies have indicated that a genetic variant (rs2304297) in the alpha(α)6 nicotinic acetylcholine receptor (nAChR) subunit, encoded by the 6 gene, may play a key role in adolescent nicotine addictive behavior. We hypothesized that the polymorphism selectively enhances nicotine + cue-primed reinstatement, but not nicotine- or cue-reinstatement in α6 (risk) vs. α6 (non-risk) allele carriers, without having baseline effects on natural rewards.

Male and Female Sprague Dawley Rats Exhibit Equivalent Natural Reward, Nicotine Self-Administration, Extinction, and Reinstatement During Adolescent-Initiated Behaviors.

Introduction: The initiation of nicotine and tobacco use peaks during adolescence. How adolescent males and females differ based on the acquisition of nicotine use and nicotine-seeking behavior is less understood. Our current studies develop a preclinical intravenous self-administration and reinstatement paradigm in male and female Sprague Dawley rats to evaluate how sex impacts the acquisition of nicotine self-administration and nicotine-seeking, when behavior is initiated during adolescence.

Use of QSPR Modeling to Characterize In Vitro Binding of Drugs to a Gut-Restricted Polymer.

Purpose: Polymeric drugs, including patiromer (Veltassa®), bind target molecules or ions in the gut, allowing fecal elimination. Non-absorbed insoluble polymers, like patiromer, avoid common systemic drug-drug interactions (DDIs). However, the potential for DDI via polymer binding to orally administered drugs during transit of the gastrointestinal tract remains.