University of Florida neuroscientists have made a mechanistic discovery that could lead to new treatment approaches for methamphetamine addiction. In a preclinical study reported in Science Signaling, a McKnight Brain Institute team led by Dr. Habibeh Khoshbouei examined the role of neuroinflammation in meth addiction. “Unlike alcohol or opioids, there currently is no medicinal therapeutic approach for methamphetamine addiction,” said Khoshbouei, a professor of neuroscience and psychiatry.
The findings reveal a previously unknown sequence of reactions in the brain involving meth-induced spikes of dopamine and a key signaling protein, tumor necrosis factor-alpha (TNF), a regulator of both acute and chronic inflammation. In mouse brain specimens, investigators uncovered a surprising dynamic interplay: meth not only increased the release of dopamine but also unexpectedly stimulated TNF. The researchers were then able to mitigate these effects using a chemical compound to target either the dopamine transporter protein or the signaling of TNF.
Drug-Seeking Behavior and Dopamine
Using electrophysiological recordings, researchers found that TNF increases firing activity of dopaminergic neurons. “And if you block the target of methamphetamine or the receptor for TNF, you block the effect of either methamphetamine or TNF,” Khoshbouei explained. This is significant because there are already FDA-approved medicines on the market that can inhibit the effects of TNF, such as those used for autoimmune disorders like Crohn’s disease.
Dr. Marcelo Febo, co-author and associate professor of psychiatry, noted: “In the case of methamphetamine, it seems like not only does meth increase inflammation, which involves the presence of immune cells and the release of TNF, but TNF itself evokes the release of dopamine, and that’s fascinating.” The hope is that the findings could open the door to new treatment targets to reduce cravings and drug-seeking behavior as well as neuroinflammatory effects associated with meth use. “This is a huge first step to show that there’s a dopaminergic target for TNF,” Febo said, adding that the results imply that modulating dopamine levels could alleviate addictive properties.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://www.mainstreetdailynews.com/health/uf-finding-treatment-meth-addiction