Medical Student Mayo Clinic Rochester Rochester, Minnesota, United States
Disclosure(s):
Abhi Goyal: No financial relationships to disclose
Introduction: Alcohol abuse is an extremely prevalent problem. Chronic ethanol (EtOH) intake increases tonic extracellular dopamine (DA) concentrations throughout the limbic system, contributing to addiction. Tracking these tonic DA changes in real-time with high spatiotemporal resolution will enable investigations into the effects of EtOH administration, and the potential of neuromodulation to reverse these tonic DA increases. Our lab has developed the multifunctional-apparatus-for-voltammetry, electrophysiology, and neuromodulation recording device that measures tonic neurotransmitter concentrations with multiple-cyclic-square-wave-voltammetry (M-CSWV) simultaneously with electrophysiological recordings and electrical stimulation across 4 channels. This allows the ability to track tonic DA concentrations changes in several brain regions in response to acute EtOH administration and neuromodulation.
Methods: Carbon-fiber-microelectrodes were lowered into the nucleus accumbens of urethane-anesthetized Sprague-Dawley rats. After one hour of baseline electrochemical recording, EtOH was administered (2.5 g/kg, i.p.). To capture the entire time course of the EtOH, 3 hours of tonic DA measurements were performed. 30 minutes after EtOH administration, electrical stimulation (90Hz, biphasic 200us pulse-width, 0.2mA) was delivered continuously to the ventral tegmental area (VTA) for 30 minutes, and the resulting effects on tonic DA levels were recorded.
Results: Tonic extracellular DA concentrations increased in the nucleus accumbens to 200%±15% of baseline after acute EtOH administration (n=4). 90Hz electrical stimulation of the VTA reversed this increase, such that DA levels during VTA stimulation were not significantly different from pre-EtOH treatment (p>0.1; n=3). After electrical stimulation was discontinued, the tonic DA levels continued to rise, and returned to 200%±12% of baseline (n=3).
Conclusion : VTA electrical stimulation reversed the acute DA increase caused by EtOH exposure, suggesting that tonic VTA stimulation may activate D2 autoreceptors, inhibiting VTA output. These results suggest the exciting possibility that DBS of this area can modulate and may be a treatment for alcoholism. We are now working to assess this possibility in chronic addiction rat models.
