Rivastigmine does not alter cocaine-induced subjective effects or self-administration

• Published in: Pharmacology, biochemistry and behavior Vol. 185; p. 172758
• Main Authors: Patel, M., Verrico, C.D., De La Garza, R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2019
• Subjects: Acetylcholine; Acetylcholinesterase inhibitors; Addiction; Adult; Analysis of Variance; Behavior, Addictive - drug therapy; Blood Pressure - drug effects; Cholinesterase Inhibitors - administration & dosage; Cholinesterase Inhibitors - adverse effects; Cholinesterase Inhibitors - pharmacology; Cocaine; Cocaine - administration & dosage; Cocaine - pharmacology; Cocaine-Related Disorders - drug therapy; Donepezil; Dopamine Uptake Inhibitors - administration & dosage; Dopamine Uptake Inhibitors - pharmacology; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heart Rate - drug effects; Humans; Huperzine A; Infusions, Intravenous; Male; Mesolimbic pathway; Middle Aged; Rivastigmine; Rivastigmine - administration & dosage; Rivastigmine - adverse effects; Rivastigmine - pharmacology; Self Administration; Stimulants; Visual Analog Scale; Stimulants; Addiction; Rivastigmine; Donepezil; Mesolimbic pathway; Acetylcholinesterase inhibitors; Acetylcholine; Cocaine; Huperzine A
• ISSN: 0091-3057; 1873-5177; 1873-5177
• DOI: 10.1016/j.pbb.2019.172758

Acetylcholinergic (ACh) neurons interface with the mesolimbic dopamine pathway implicated in addiction, and acetylcholinesterase inhibitors (AChEis) have been shown to reduce the immediate effects of cocaine and amount used. Our study is the first to examine if the safe and low-interaction AChEi rivastigmine (riv) alters the subjective effects produced by cocaine administration. Cocaine-dependent subjects were randomized to daily placebo, riv 3 mg, or riv 6 mg, administered inpatient for 10 days. On day 1 (pre-dose) and day 9, subjects received both IV cocaine 40 mg or placebo in a randomized order with subsequent serial assessments of visual analog scale (VAS) subjective effects and pharmacokinetic measurements. On day 10 all participants received one baseline dose of cocaine 20 mg with assessment of subjective effects, and were then able to purchase additional doses at 15 min intervals with study earnings. 40 subjects were randomized to placebo (n = 16), riv 3 mg (n = 13), or riv 6 mg (n = 12). All subjects completed the study and there were no demographic differences between treatment groups. Pre- and post- treatment, there were no significant pharmacokinetic differences (blood levels of cocaine, BE, EME) following cocaine administration. In a two-way ANOVA, IV cocaine significantly increased positive VAS category ratings compared to placebo, but rivastigmine treatment at either dose had no significant effect on any VAS category ratings. Similarly, there was no significant rivastigmine effect on any category in the day 10 cocaine administration, and no effect on number of subsequent doses participants purchased. Rivastigmine 3 or 6 mg had no significant effect on the subjective effects of cocaine after 9 days of treatment. This is an important finding as other drugs in the AChEi class (donepezil, Huperzine A) have produced significant results, but differ in their receptor specificity and PK parameters. •Intravenous cocaine significantly increased positive VAS category ratings.•Rivastigmine did not alter cocaine-induced subjective effects.•Rivastigmine had no significant effect on choices for cocaine.