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
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.
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