Breakthrough in pharmacological treatment for drug abuse

Related tags Dopamine

A team of scientists in the US have identified a molecular target
in which could herald the formation of the first pharmacological
therapy for treating amphetamine addiction, which is estimated to
affect around 9 million Americans, writes Wai Lang Chu.

They have identified a chemical modification during the release of the neurotransmitter dopamine in the presence of amphetamine that could lead to the design and synthesis of new therapeutics, such as a drug that blocks the effects of amphetamine-like psychostimulants without inhibiting the normal regulation of the neurotransmitter in nerve cells.

Currently, there are no pharmacological treatments for amphetamine dependence. Antidepressant medications can be used to combat the depressive symptoms of withdrawal but the most effective treatment for amphetamine addiction at present is cognitive behavioural intervention.

Led by Jonathan Javitch and Aurelio Galli at the University of Columbia, New York, the research team have identified a chemical modification of the dopamine transporter (DAT), related to the degree of phosphorylation of a portion of the molecule that resides inside the cell membrane.

The implication is that drugs could be designed to block this change, and thereby inhibit the effect of amphetamine in stimulating dopamine release from the DAT.

In the normal situation, DAT is involved in terminating dopamine signalling by removing the dopamine chemical messenger molecules from the junctions between nerves and returning them into the releasing neurons (reuptake).

Amphetamine has a double effect on this system. It inhibits reuptake and stimulates dopamine release from the nerve ending, so dopamine accumulates in the junction and the dopaminergic signal gets stronger.

The researchers speculate that inhibiting the phosphorylation change in the DAT caused by amphetamine could stop it causing dopamine release from the neuron, but without blocking the DAT's ability to take up and recycle dopamine from the nerve junction.

The net result of this is that the dopamine signal will go down, inhibiting the effects of dopamine on the reward centres of the brain without interfering with normal dopamine clearance.

The research is published in the journal PLoS Biology​.

Related topics Preclinical Research

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