The Reinforcing and Rewarding Effects of Methylone, a Synthetic Cathinone Commonly Found in "Bath Salts" - PubMed (original) (raw)

The Reinforcing and Rewarding Effects of Methylone, a Synthetic Cathinone Commonly Found in "Bath Salts"

Lucas R Watterson et al. J Addict Res Ther. 2012.

Abstract

Methylone is a member of the designer drug class known as synthetic cathinones which have become increasingly popular drugs of abuse in recent years. Commonly referred to as "bath salts", these amphetamine-like compounds are sold as "legal" alternatives to illicit drugs such as cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy). Following their dramatic rise in popularity along with numerous reports of toxicity and death, several of these drugs were classified as Schedule I drugs in the United States in 2012. Despite these bans, these drugs and other new structurally similar analogues continue to be abused. Currently, however, it is unknown whether these compounds possess the potential for compulsive use and addiction. The present study sought to determine the relative abuse liability of methylone by employing intravenous self-administration (IVSA) and intracranial self-stimulation (ICSS) paradigms in rats. We demonstrate that methylone (0.05, 0.1, 0.2, and 0.5 mg/kg/infusion) dose-dependently functions as a reinforcer, and that there is a significant positive relationship between methylone dose and reinforcer efficacy. Furthermore, responding during short access sessions (ShA, 2 hr/day) appeared more robust than previous IVSA studies with MDMA. However, unlike previous findings with abused stimulants such as cocaine or methamphetamine, long access sessions (LgA, 6 hr/day) did not lead to escalated drug intake or increased reinforcer efficacy. Finally, methylone produced a dose-dependent, but statistically non-significant, trend towards reductions in ICSS thresholds. Together these results reveal that methylone may possess an addiction potential similar to or greater than MDMA, yet patterns of self-administration and effects on brain reward function suggest that this drug may have a lower potential for abuse and compulsive use than prototypical psychostimulants.

Keywords: Intracranial self-stimulation; Methylone; Monoamine; Reinforcement; Reward; Self-administration; Stimulant.

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Figures

Figure 1

Figure 1

Intravenous self-administration (IVSA) of methylone. Data presented are active and inactive lever presses across the first 21 days of IVSA sessions for the (a) 0.05 (b) 0.1 (c) 0.2 and (d) 0.5 mg/kg/infusion groups (n = 12 for 0.05 and 0.5 mg/kg/infusion groups; n = 11 for the 0.1 and 0.2 mg/kg/infusion groups). *p<0.05 between active and inactive lever presses.

Figure 2

Figure 2

(a) Total number of infusions obtained during the first 21 days of 2 hr daily access sessions for each dose of methylone tested (n=12 for 0.05 and 0.5 mg/kg/infusion groups; n = 11 for the 0.1 and 0.2 mg/kg/infusion groups). (b) Percent of animals at or above criterion (10 active lever presses per session) for each experimental session.

Figure 3

Figure 3

Total number of infusions earned during progressive ratio (PR) tests following 21 days of ShA sessions (ShA PR) and 10 days of LgA sessions (LgA PR) for the 0.05, 0.1, 0.2, and 0.5 mg/kg/infusion groups (n = 12 for 0.05 and 0.5 mg/kg/infusion groups; n = 11 for the 0.1 and 0.2 mg/kg/infusion groups). *p<0.05 compared to the 0.05, 0.1, and 0.2 mg/kg/infusion dose groups. (b) Total number of infusions obtained during the 10 days of LgA IVSA sessions for each dose of methylone tested (n=10 for 0.05 and 0.5 mg/kg/infusion groups; n = 11 for the 0.1 and 0.2 mg/kg/infusion groups).

Figure 4

Figure 4

Effects of saline vehicle and methylone (0.1, 0.5, 1, 3, 5, and 10 mg/kg, i.p.) on intracranial self-stimulation (ICSS) current-intensity thresholds (n=4).

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