Surprisingly, the researchers reported, treating mice lacking dopamine with high doses of amphetamine derivatives ?including methamphetamine and MDMA, otherwise known as Ecstasy ?reversed those symptoms. Ecstasy was most effective at counteracting the manifestations of Parkinson's symptoms in the mice, with the beneficial effects becoming more pronounced with increasing dose.
The researchers also report that low doses of amphetamines could, when combined with L-DOPA, potentiate minimally effective doses of L-DOPA in the mice. This could have important considerations in reducing some of the side effects of current therapy.
"The locomotor stimulating effect of amphetamine and its derivatives are classically thought to result from a massive flood of dopamine," said Sotnikova. "However, the mice have only a tiny fraction of dopamine, which cannot be recycled, precluding a rise in dopamine as the possible mechanism.
"Taken together, the findings indicate that Ecstasy can improve movement control independently of dopamine and, most importantly provide evidence that drug activation of other neuronal pathways may be sufficient to restore movement even in the virtual absence of dopamine neurotransmission," she added.
Amphetamines might reverse the animal's symptoms through their effects on a different group of receptors called trace amine receptors, the researchers suggested. Recent evidence showed that amphetamines act on trace amine receptors in addition to dopamine transmission, yet little is known about their physiological role in mammals.
The current findings are particularly promising given the severity of symptoms in the mice completely lacking dopamine, said Gainetdinov. "We think that this new animal model provides a much more stringent test for potential drugs that might prove eff
Source:Duke University Medical Center