M. Foster Olive
Arizona State University, USA
M. Foster Olive completed his Ph.D. at the age of 28 years from the University of California at Los Angeles and conducted postdoctoral studies at Stanford University School of Medicine and the University of California at San Francisco. He is a member of the faculty of the Behavioral Neuroscience program in the Department of Psychology at Arizona State University. He has published more than 75 papers in reputed journals and serves as an editorial board member of the Journal of Addiction Research and Therapy, the Open Addiction Journal, and CNS & Neurological Disorders – Drug Targets.
Synthetic cathinones are a class of designer drugs comprised of various amphetamine-like stimulants including 4-methylmethcathinone (mephedrone) and methylenedioxypyrovalerone (MDPV). These compounds produce psychostimulant effects by inhibiting presynaptic dopamine and norepinephrine transporters, and the desired psychological effects of these drugs include euphoria, empathogenesis, and increased alertness and arousal. However, in recent years, there has been drastic increase in the number cases of adverse toxic effects of synthetic cathinones including tachycardia, hypertension, hyperthermia, psychosis, extreme agitation, violence, and death. The patterns of habitual use or abuse of synthetic cathinones and their potential for addiction have not been well-studied. We therefore sought to determine the reinforcing effects of MDPV using intravenous self-administration in rodents. We also examined the effects of increasing behavioral demand on MPDV self-administration under a progressive ratio schedule of reinforcement. Male Sprague-Dawley rats were implanted with jugular vein catheters and then allowed to acquire intravenous self-administration of MPDV at doses of 0.05, 0.1 or 0.2 mg/kg per infusion. Rats were first allowed 10 days of self-administration of MDPV under an FR1 schedule of reinforcement in daily 2 hr sessions. Rats then underwent testing under a progressive ratio (PR) schedule of reinforcement in a 16 hr overnight session. Next, for half of the animals, the length of the self-administration session was increased to 6 hr (long access, LgA), while for the other half of the animals the session length remained at 2 hr (short access, ShA). A total of 10 additional ShA or LgA access sessions were conducted. Under both ShA and LgA conditions, rats demonstrated robust self-administration of MDPV. An inverse relationship between MDPV dose and the number of infusions obtained per session was observed, and a linear relationship between MDPV dose and the number of infusions obtained under PR testing was observed. Following 10 days of extended access to MDPV, rats self-administering the 0.1 and 0.2 mg/kg showed 59% and 23% increases in MPDV intake, respectively. Our findings indicate that MDPV is a potent reinforcer when self-administered intravenously, and produces rates of responding under ShA and PR conditions similar to those observed in rats self-administering methamphetamine. In addition, rats self-administering the higher doses MDPV demonstrated escalation of intake following extended access to the drug. Additional studies examining the effects of MDPV on brain stimulation reward are currently underway. Our findings suggest a potential for abuse of and/or addiction to MDPV, which carries significant implications for the addiction community as well as future drug policy. This work was supported by NIH grant DA025606.