Effects in Laboratory Animals

The acute effects of MDMA have been investigated in a diverse range of laboratory animal species. A key consideration in utilizing animal models is in establishing appropriate species-equivalent dosing levels to model human MDMA use (Green et al. 2009). This issue is still far from resolved with many animal studies using MDMA dose regimes that are in the extreme range. Species-specific ► pharmacokinetics also complicate the picture.

MDMA has amphetamine-like sympathomimetic effects, increasing blood pressure and heart rate. It exerts a powerful influence on body temperature, with the direction of change (hyperthermia or ► hypothermia) dependent upon the ambient temperature of the environment (Green et al. 2003). The hyperthermic response to MDMA appears in part to be reliant upon the mitochondrial uncoupling protein 3 (UCP-3) acting in striated myocytes. MDMA also produces peripheral vasoconstriction, further preventing heat loss.

Behaviorally, MDMA causes amphetamine-like ► hyperactivity and locomotor ► sensitization in rodent species. ► Intravenous self-administration of MDMA is seen in mice, rats, and nonhuman primates although rates are significantly less than that of other abused drugs such as the ► psychostimulants cocaine and methamphet-amine. Self-administration of MDMA in rats is increased at high ambient temperatures, and this may be in part due to augmentation of MDMA-stimulated increases in do-pamine and neuronal activation in reward-relevant brain regions. Rats will also show a ► conditioned place preference to MDMA, an effect that involves dopamine, ► opi-oid, and ► endocannabinoid systems.

In line with its characteristic prosocial effects in humans, MDMA reduces aggression and increases social interaction in rodents. In the ► social interaction test, rats spend increased times in adjacent contact following acute MDMA treatment, and this effect is also augmented at high ambient temperatures. This prosocial effect of MDMA is reduced by oxytocin antagonists and is minimicked by the

► 5-HT1A agonist 8-OH-DPAT (McGregor et al. 2008).

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