Effects of alpha-Pyrrolidinovalerophenone 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., & Olive, M. F. (2015). Effects of alpha-Pyrrolidinovalerophenone 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(01).
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 (0.1-5mg/kg) and 4-methyl-N-ethcathinone (1-100mg/kg) on brain reward function. Methamphetamine (0.1-3mg/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 (1mg/kg) produced a significant maximal reduction in intracranial self-stimulation thresholds (~19%) most similar to maximal reductions produced by methamphetamine (1mg/kg, ~20%). Maximal reductions in intracranial self-stimulation thresholds produced by 4-methyl-N-ethcathinone were observed at 30mg/kg (~15%) and were comparable with those observed with methamphetamine and alpha-pyrrolidinopentiophenone tested at the 0.3-mg/kg dose (~14%). Additional analysis of the ED50 values from log-transformed data revealed the rank order potency of these drugs as methamphetamine approximately 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