Investigating sex differences and the effect of drug exposure order in the sensory reward-enhancing effects of nicotine and d-amphetamine alone and in combination

• Published in: Neuropharmacology Vol. 202; p. 108845
• Main Authors: McNealy, Kathleen R., Houser, Sydney D., Barrett, Scott T., Bevins, Rick A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2022
• Subjects: Adderall; ADHD; Animals; Conditioning, Operant; Dexedrine; Dextroamphetamine - administration & dosage; Dextroamphetamine - adverse effects; Drug Combinations; Female; Humans; Male; Nicotine - administration & dosage; Nicotine - adverse effects; Operant; Polysubstance use; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Reward; Sex Characteristics; Smoking; Substance-Related Disorders; ADHD; Polysubstance use; Dexedrine; Operant; Adderall; Smoking
• ISSN: 0028-3908; 1873-7064; 1873-7064
• DOI: 10.1016/j.neuropharm.2021.108845

Nicotine enhances the rewarding effects of other environmental stimuli; this reward-enhancement encourages and maintains nicotine consumption. Nicotine use precedes other psychostimulant use, but receiving a stimulant prescription also predicts future smoking. Previously, no study has investigated effects of drug exposure order in reward-enhancement, nor with nicotine and d-amphetamine. Thus, we aimed to investigate how drug exposure order impacted the reward-enhancing effects of nicotine and d-amphetamine, alone and in combination. We used 20 male and 20 female Sprague-Dawley rats. Enhancement was investigated within-subjects by examining responding maintained by a visual stimulus reinforcer following a pre-session injection of either d-amphetamine (Sal, 0.1, 0.3, or 0.6 mg/kg) or nicotine (Sal, 0.03, 0.06, 0.1, 0.3 mg/kg). Twenty rats (10 M, 10 F) completed enhancement testing with nicotine before d-amphetamine. The other 20 rats (10 M, 10 F) completed testing with d-amphetamine before nicotine. Following these phases, rats were then given two pre-session injections: one of d-amphetamine (Sal, 0.1, 0.3, or 0.6 mg/kg) and another of nicotine (Sal, 0.03, 0.06, 0.1, or 0.3 mg/kg). Experiencing amphetamine before nicotine increased reward-enhancing effects of nicotine. Females exhibited greater effects of d-amphetamine on reward-enhancement, with no effect of exposure order. During the interaction phase, receiving nicotine before amphetamine enhanced the interaction between nicotine and d-amphetamine for females whereas amphetamine before nicotine heightened this interaction for males. From this, prior and current amphetamine use, in addition to sex, should be considered when treating nicotine dependency and when examining factors driving poly-substance use involving nicotine and d-amphetamine. Keywords: Adderall, ADHD, Dexedrine, operant, smoking, polysubstance use. •Female rats exhibited greater reward-enhancing effects of d-amphetamine.•There were no sex differences in reward-enhancement by any nicotine dose.•Experiencing amphetamine before nicotine increased the reward-enhancing effects of nicotine alone independently of sex.•Receiving nicotine before amphetamine increased the interaction between nicotine and d-amphetamine on reward-enhancement for females.•Receiving amphetamine before nicotine heightened the interaction between nicotine and d-amphetamine for males.