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

Abstract

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, α-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 α-pyrrolidinopentiophenone and 4-methyl-N-ethcathinone produced significant intracranial self-stimulation threshold reductions similar to that of methamphetamine. α-Pyrrolidinopentiophenone (1 mg/kg) produced a significant maximal reduction in intracranial self-stimulation thresholds (~19%) most similar to maximal reductions produced by methamphetamine (1 mg/kg, ~20%). Maximal reductions in intracranial self-stimulation thresholds produced by 4-methyl-N-ethcathinone were observed at 30 mg/kg (~15%) and were comparable with those observed with methamphetamine and α-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 ≈ α-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.

Keywords: ICSS; abuse liability; bath salts; psychostimulants; synthetic cathinones.

Figure 1.

Chemical structures of the traditional psychostimulants methamphetamine (METH) and methylenedioxymethamphetamine (MDMA), first-generation synthetic cathinones methylenedioxypyrovalerone (MDPV) and methylone, and second-generation synthetic cathinones α‐pyrrolidinopentiophenone (α-PVP) and 4-methyl-N-ethcathinone (4-MEC).

Figure 2.

Effects of the second-generation synthetic cathinone (A) 4-methyl-N-ethcathinone (4-MEC) (1, 3, 10, 30, mg/kg), (B) α‐pyrrolidinopentiophenone (α-PVP) (0.1, 0.3, 1, and 3mg/kg), and the traditional psychostimulant (C) methamphetamine (METH) (0.1, 0.3, 1, and 3mg/kg) on intracranial self-stimulation (ICSS) thresholds. Data represent mean±95% confidence interval and are expressed as a percent change in ICSS thresholds relative to the previous baseline session. N=5, 5, and 4 in A, B, and C, respectively. *Symbols represent P<.05 vs. saline. In C, the confidence interval upper limit (no shown) for the 3-mg/kg dose=153.87.