A comparison of MDMA (Ecstasy) and 3,4-methylenedioxymethcathinone (Methylone) in their acute behavioural effects and development of tolerance in rats (2016)
AuthorsDavidson, Mark L.show all
Methylone (3,4-methylenedioxymethcathinone), the β-ketone analogue of the popular party drug MDMA (3,4-methylenedioxymethamphetamine, “ecstasy”), is a relatively new designer drug that is reported to have similar subjective effects and psychopharmacological properties to MDMA. However, unlike MDMA, little is known about the acute behavioural effects or the effects of repeated use of this drug. The goal of the current thesis was to investigate the behavioural effects of methylone and compare these to the effects of MDMA using an animal model. The second aim was to determine whether there was evidence of behavioural sensitisation or tolerance to methylone with repeated exposure. To achieve this, 108 male and female PVG/c hooded rats (6M and 6F per group) were administered various doses of MDMA or methylone (2.5, 5, 8, 12mg/kg), or saline vehicle (i.p.). The behavioural effects of these drugs were examined 20 m later, including horizontal locomotor activity, rearing behaviour, and central occupancy of an open field, anxiety behaviours in a light/dark box, and working memory in a novel object recognition task. The results showed that MDMA and methylone administration produce similar, but not identical, behaviours. Methylone was shown to produce greater psychostimulant effects, while MDMA produced more toxic effects. Female rats demonstrated greater psychostimulant effects than males, while males had higher rates of lethality. In order to assess the effects of repeated drug use, one week after binge-type drug administration of MDMA or methylone (5 mg/kg for 3 doses every 1h on 2 consecutive days), open field and light/dark box testing was repeated following a further 5 mg/kg challenge of drug. There was no evidence of locomotor sensitisation in the open field, although females showed sensitisation in rearing activity. These findings suggest that methylone may produce less toxic, but more stimulant, effects than MDMA. Methylone may therefore be a cocaine-MDMA mixed psychostimulant, both in a psychopharmacological and a behavioural sense.