Transcranial direct current stimulation restores addictive behavior via prefrontal-striatal circuit

Area of Science:

• Neuroscience
• Addiction Research
• Brain Stimulation

Background:

• Methamphetamine (METH) dependence is a severe brain disorder with high relapse rates.
• Current treatments for METH addiction have limited efficacy, and neural mechanisms of relapse are not fully understood.
• Transcranial direct current stimulation (tDCS) shows potential for addiction treatment, but its underlying neural basis requires elucidation.

Purpose of the Study:

• To investigate the neural circuit mechanisms by which tDCS modulates METH-induced addictive behavior and relapse.
• To determine if tDCS applied to the medial prefrontal cortex (mPFC) can prevent METH relapse in a rodent model.

Main Methods:

• Utilized a METH-conditioned place preference (CPP) paradigm in rodents.
• Integrated functional magnetic resonance imaging (fMRI), electrophysiology, chemogenetics, and in vivo fiber photometry.
• Developed a novel rodent tDCS model targeting the mPFC.

Main Results:

• tDCS applied to the mPFC effectively prevented METH relapse.
• tDCS treatment enhanced neuronal activity in both the infralimbic cortex (IL) and nucleus accumbens shell (NAcSh).
• Chemogenetic manipulation of the IL-NAcSh pathway confirmed its role in mediating tDCS effects; inhibition abolished, while activation suppressed relapse.

Conclusions:

• The IL-NAcSh pathway acts as a critical descending regulatory circuit in mediating the therapeutic effects of tDCS for METH addiction.
• These findings provide novel insights into circuit-based neuromodulatory treatments for substance use disorder.
• tDCS targeting the mPFC presents a promising therapeutic strategy for preventing relapse in METH dependence.