Acupuncture inhibits GABA neuron activity in the ventral tegmental area and reduces ethanol self-administration.
BACKGROUND
Withdrawal from chronic ethanol enhances ventral tegmental area (VTA) GABA neuron excitability and reduces mesolimbic dopamine (DA) neurotransmission, which is suppressed by acupuncture at Shenmen (HT7) points (Zhao et al., 2006). The aim of this study was to evaluate the effects of HT7 acupuncture on VTA GABA neuron excitability, ethanol inhibition of VTA GABA neuron firing rate, and ethanol self-administration. A role for opioid receptors (ORs) in ethanol and acupuncture effects is also explored.


METHODS
Using electrophysiological methods in mature rats, we evaluated the effects of HT7 stimulation and opioid antagonists on VTA GABA neuron firing rate. Using behavioral paradigms in rats, we evaluated the effects of HT7 stimulation and opioid antagonists on ethanol self-administration using a modification of the sucrose-fading procedure.


RESULTS
HT7 stimulation produced a biphasic modulation of VTA GABA neuron firing rate characterized by transient enhancement followed by inhibition and subsequent recovery in 5 minutes. HT7 inhibition of VTA GABA neuron firing rate was blocked by systemic administration of the nonselective μ-opioid receptor antagonist naloxone. HT7 stimulation significantly reduced ethanol suppression of VTA GABA neuron firing rate, which was also blocked by naloxone. HT7 acupuncture reduced ethanol self-administration without affecting sucrose consumption. Systemic administration of the δ-opioid receptor (DOR) antagonist naltrindole blocked ethanol suppression of VTA GABA neuron firing rate and significantly reduced ethanol self-administration without affecting sucrose consumption.


CONCLUSIONS
These findings suggest that DOR-mediated opioid modulation of VTA GABA neurons may mediate acupuncture's role in modulating mesolimbic DA release and suppressing the reinforcing effects of ethanol.
Yang
Chae Ha
CH
Daegu Haany University, Daegu, South Korea.
Yoon
Seong Shoon
SS
Hansen
David M
DM
Wilcox
Jeffrey D
JD
Blumell
Bryan R
BR
Park
Jung Jae
JJ
Steffensen
Scott C
SC
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D015670:Acupuncture Therapy / Q000379:methods*; D000818:Animals; D004347:Drug Interactions; D004558:Electric Stimulation; D000431:Ethanol / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage; D013623:Tail / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D009270:Naloxone; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D013395:Sucrose; D009271:Naltrexone; C055382:naltrindole