Methylphenidate Produces Conditioned place preference, and cannabidiol Exposure during Extinction does not Inhibit the Reinstatement of Methylphenidate in the Marmoset Monkeys

Abstract

Methylphenidate (MPH) is a central nervous system stimulant used as a pharmacotherapy to treat Attention-Deficit/Hyperactivity Disorder and narcolepsy. Scientists are concerned that MPH use could lead to increase the risk of vulnerability to drug abuse later in life. Little work has been carried out on the addictive potential of MPH in non-human primates (NHP). In the present study we intend to evaluate whether the MPH is able to produce a conditioned response and if the exposure to cannabidiol (CBD) during the extinction trial of the conditioned preference place (CPP) paradigm can inhibit the reinstatement of the response in male marmoset monkeys. Animals received alternating intraperitoneal (i.p.) injections of either MPH (5mg/kg) or saline (SAL) to a daily 15 min conditioning trial during 10 consecutive days in drug- and saline-paired compartments, respectively, of a CPP box. After a place preference test the animals were submitted to daily CBD injection in a 15min extinction trial, until the association between MPH and the MPH-paired compartment was extinguished. Then, 24h after the last extinction trial, animals received a priming dose of MPH (1mg/kg) and were submitted to a 15min retest trial. We found that MPH induced strong and long-lasting reinforcing properties during the conditioning period even after extinction training and reinstatement test. Therefore, MPH induced a CPP response in a NHP model and CBD administration could not inhibit the reinstatement of the MPH-induced CPP response.