Effects of α-Pyrrolidinopentiophenone and 4-Methyl-N-Ethylcathinone, Two Synthetic Cathinones Commonly Found in Second-Generation Bath Salts, on Intracranial Self-Stimulation Thresholds in Rats

Background: Use of synthetic cathinones, which are designer stimulants found in bath salts, has increased dramatically in recent years. Following governmental bans of methylenedioxypyrovalerone, mephedrone, and methylone, a second generation of synthetic cathinones with unknown abuse liability has emerged as replacements. Methods: Using a discrete trials current intensity threshold intracranial self-stimulation procedure, the present study assessed the effects of 2 common second-generation synthetic cathinones, alpha-pyrrolidinopentiophenone (0.1-5 mg/kg) and 4-methyl-N-ethcathinone (1-100 mg/kg) on brain reward function. Methamphetamine (0.1-3 mg/kg) was also tested for comparison purposes. Results: Results revealed both alpha-pyrrolidinopentiophenone and 4-methyl-N-ethcathinone produced significant intracranial self-stimulation threshold reductions similar to that of methamphetamine. alpha-Pyrrolidinopentiophenone (1 mg/kg) produced a significant maximal reduction in intracranial self-stimulation thresholds (similar to 19%) most similar to maximal reductions produced by methamphetamine (1 mg/kg, similar to 20%). Maximal reductions in intracranial self-stimulation thresholds produced by 4-methyl-N-ethcathinone were observed at 30 mg/kg (similar to 15%) and were comparable with those observed with methamphetamine and alpha-pyrrolidinopentiophenone tested at the 0.3-mg/kg dose (similar to 14%). Additional analysis of the ED50 values from log-transformed data revealed the rank order potency of these drugs as methamphetamine approximate to alpha-pyrrolidinopentiophenone > 4-methyl-N-ethcathinone. Conclusions: These data suggest that the newer second-generation synthetic cathinones activate the brain reward circuitry and thus may possess a similar degree of abuse potential as prototypical illicit psychostimulants such as methamphetamine as well as the first generation synthetic cathinone methylenedioxypyrovalerone, as previously reported.