Abstract
Synthetic cathinones are designer psychostimulants that are derivatives of the natural alkaloid cathinone, and produce effects similar to more traditional illicit stimulants such as cocaine and methamphetamine. The pyrovalerone cathinones methylenedioxypyrovalerone (MDPV) and α-pyrrolidinopropiophenone (α-PPP) exert their effects via inhibition of presynaptic dopamine and norepinephrine reuptake transporters. While the reinforcing effects of MDPV in rodents are well-established, very few studies have examined self-administration patterns of α-PPP. Users of synthetic cathinones often engage in repeated binge episodes of drug intake that last several days. We therefore sought to determine the reinforcing effects of three doses of α-PPP (0.05, 0.1 and 0.32 mg/kg/infusion) under conditions of prolonged binge-like access conditions, with three 96-h periods of drug access interspersed with 72 h of abstinence. MDPV (0.05 mg/kg/infusion) was used as a comparison drug. Our results show that both MDPV and the high (0.32 mg/kg/infusion) dose of α-PPP are readily self-administered at high levels across all three extended access periods, whereas lower doses of α-PPP produce variable and less robust levels of self-administration. These results indicate that higher doses of α-PPP have reinforcing effects under conditions of extended access, suggesting the potential for abuse and a need for consideration in drug control policies.
Highlights
Referred to as “bath salts”, synthetic cathinones are psychostimulants with neurochemical actions similar to those of cocaine and methamphetamine [1]
Data from n = 4 rats were excluded from analysis due to loss of catheter patency, and data from n = 5 rats were excluded from analysis due to failure to meet acquisition criteria (>100 infusions obtained during the first 96-h period, and/or failure to discriminate active vs. inactive nosepoke hole by a ratio of >1:1)
Self-administration of a-PPP above levels observed for saline were variable and dosedependent, as reliable self-administration was only observed at the highest dose tested (0.32 mg/kg/infusion)
Summary
Referred to as “bath salts”, synthetic cathinones are psychostimulants with neurochemical actions similar to those of cocaine and methamphetamine [1]. Among the first cathinone derivatives to infiltrate drug markets in the 21st century were the so-called “first generation” synthetic cathinones that included 3,4-methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and methylone. The pharmacological mechanisms of action of synthetic cathinones are similar in nature to those exerted by traditional psychostimulants [4, 6]. 4-methylmethcathinone (mephedrone) produces amphetamine-like monoamine releasing effects via inhibition and reversal of presynaptic transporters for norepinephrine and dopamine (NET and DAT, respectively) as well as the type 2 vesicular monoamine transporter (VMAT2). MDPV, a-PVP and a-PPP produce cocaine-like inhibition of DAT and NET, with up to 100 times greater potency than cocaine and with longer durations of action [7, 8]
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