Effects of alpha-Pyrrolidinopentiophenone and 4-Methyl-N-Ethylcathinone, Two Synthetic Cathinones Commonly Found in Second-Generation "Bath Salts," on Intracranial Self-Stimulation Thresholds in Rats
Watterson, L. R., Burrows, B. T., Hernandez, R. D., Moore, K. N., Grabenauer, M., Marusich, J. A., & Olive, M. F. (2015). Effects of alpha-Pyrrolidinopentiophenone and 4-Methyl-N-Ethylcathinone, Two Synthetic Cathinones Commonly Found in Second-Generation "Bath Salts," on Intracranial Self-Stimulation Thresholds in Rats. International Journal of Neuropsychopharmacology, 18(1). DOI: 10.1093/ijnp/pyu014
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.