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Insulin Clue for Amphetamine Abuse Treatment

Rat study shows hypoinsulinemia depletes effect of the drug

MONDAY, Oct. 22 (HealthDay News) -- Rats that have been depleted of insulin self-administer less amphetamine compared with those with normal insulin levels, which suggests a potential new mechanism for treatment of amphetamine abuse through insulin signaling pathways, according to a study published online Oct. 16 in PLoS Biology.

Jason M. Williams, Ph.D., of Vanderbilt University Medical Center in Nashville, Tenn., and colleagues conducted a study in rats to show how striatal protein kinase function and dopamine transporter cell-surface expression are significantly reduced by the diabetogenic agent streptozotocin.

In rats that were insulin-deficient, the response to amphetamine was severely reduced and the drug evoked less dopamine efflux due to selective inhibition of the insulin downstream effector phosphotidylinositol 3-kinase (P13K), the authors write.

"The present studies establish that P13K signaling regulates the neurochemical actions of amphetamine-like psychomotor stimulants," they conclude. "These data suggest that insulin signaling pathways may represent a novel mechanism for regulating dopamine transmission, one which may be targeted for the treatment of amphetamine abuse and potentially other dopaminergic disorders."

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