Reinforcing Effects of Phenethylamine Analogs Found in Dietary Supplements

Abstract

HYPOTHESIS Phenethylamine analogs are often found in dietary supplements, even though they are rarely listed on the ingredient label. Due to their structural similarities to amphetamine, it is anticipated that these compounds display comparable pharmacological effects to amphetamine and other stimulants. Here, we compared the effects of amphetamine and selected phenethylamine analogs on drug self-administration behavior in rats. METHODS Male Sprague-Dawley rats fitted with intravenous (i.v.) jugular catheters were placed in experimental chambers containing two nose poke holes. Active nose poke responses resulted in delivery of a constant volume of drug (0.2 mL) over a period of 2 s on a fixed-ratio 1 schedule, followed by a 20 s timeout. Acquisition doses for the compounds were 0.1 mg/kg/inj amphetamine, 1 mg/kg/inj a-ethylphenethylamine (AEPEA) and N,a-diethylphenethylamine (DEPEA), and 3 mg/kg/inj b-methylphenethylamine (BMPEA). Following 10 days of acquisition training, dose-effect testing began with three additional doses, each of which were tested for 3 days. Subjects then returned to the original training dose until responses stabilized. RESULTS At the end of acquisition training, all four compounds showed a significant difference in active versus inactive nose pokes (p<0.0001), indicating that subjects acquired drug self-administration. During dose-effect testing, all the drugs showed a typical inverted dose-effect function, although there were clear differences in potency. Maximum responding was maintained at 0.03 mg/kg/inj for amphetamine, 0.3 mg/kg/inj for DEPEA and AEPEA and over 1 mg/kg/inj for BMPEA. AEPEA and DEPEA appeared to maintain higher rates of responding than amphetamine, potentially reflecting differences in duration of action. Self-administration of BMPEA occurred despite BMPEA showing minimal locomotor stimulating effects in a previous experiment. CONCLUSION Direct comparisons between the three phenethylamine analogs and amphetamine show that these compounds support self-administration, indicating that dietary supplements containing these compounds could have significant abuse liability.