Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation
733—Cocaine Reinforcement, Seeking, and Reinstatement I
Wednesday, November 13, 2013, 8:00 am - 12:00 noon
733.25: Acupuncture increases GABA release in the ventral tegmental area and reduces cocaine-seeking behavior
Location: Halls B-H
*W. JIN1, H. KIM1, B.-H. LEE2, K. KIM1, C. YANG1; 1Physiol., 2Acupuncture, Moxibustion & Acupoint, Daegu Haany Univ., Daegu, Korea, Republic of
Abstract Body: Activation of GABA neurons in the ventral tegmental area (VTA) reduces cocaine-seeking behavior and dopamine release in the nucleus accumbens (NAc). We have previously demonstrated that acupuncture at Shenmen (HT7) points suppressed stress-induced reinstatement of cocaine-seeking behavior and dopamine release in the NAc induced by a systemic cocaine challenge. Using a within-session extinction/reinstatement paradigm in rats that self-administer cocaine, we evaluated the effects of HT7 acupuncture and GABA antagonists on cocaine-primed reinstatement of cocaine- seeking behavior. Using microdialysis, we evaluated the effects of HT7 acupuncture on VTA GABA release. Acupuncture at the specific acupoint HT7 significantly attenuated the reinstatement of cocaine-seeking behavior, which was blocked by VTA infusions of the GABAB receptor antagonist saclofen. HT7 acupuncture significantly reduced cocaine suppression of VTA GABA release. These results suggest that acupuncture attenuates cocaine-seeking behavior through activation of GABA neurons in the VTA.
Lay Language Summary: Our research indicates that acupuncture therapy reduces cocaine relapse by regulating neurotransmitters in the brain through stimulation of specific sensory receptors on the skin around the Shenmen (HT7) acupuncture point. Our results present experimental evidence that acupuncture may be a solution to providing effective therapeutic intervention in cocaine addiction. Cocaine addiction is characterized by chronic relapse following periods of abstinence, and remains one of the world’s foremost major public health problems. Many methods have been employed in the battle against cocaine addiction, and yet, satisfactory medical intervention to treat the high rates of cocaine craving and relapse has yet to be identified. Our research has focused on the brain’s mesolimbic dopamine pathway, widely believed to be directly responsible for reinforcing the desire in addicts to take drugs. This pathway originates from the ventral tegmental area and terminates in the nucleus accumbens. Moreover, studies have found that these neurons, whose function is to release dopamine from their terminals in the nucleus accumbens, can be inhibited by the actions of the inhibitory neurotransmitter GABA in the ventral tegmental area. We have previously examined the interaction between the stimulation of the HT7 acupuncture point and the increase in dopamine release in the nucleus accumbens that occurs when an animal subject is exposed to ethanol. We were able to show that the stimulation of the HT7 point results in an inhibition of ethanol-induced dopamine release through the GABA pathway. Given these findings, we proposed that acupuncture at the HT7 point causes GABA release in the ventral tegmental area, thereby inhibiting the activity of the dopamine neurons within the ventral tegmental area, and consequently reducing the amount of dopamine released from the nucleus accumbens, finally resulting in the behavioral effect of modulating relapse to cocaine-seeking behavior. To test this hypothesis, we introduced rats to a cocaine self-administration paradigm. After the self-administration process, we induced extinction in the rats in order to test for the effect of acupuncture on their ability to then reinstate cocaine-seeking behavior (relapse). GABA levels in the ventral tegmental area were measured using microdialysis in different groups of rats. Acupuncture was applied at bilateral HT7 points for 1 minute before exposure to cocaine. HT7 is located on the transverse crease of the wrist of the forepaw. In another group of rats, bilateral Yangxi (LI5) points, which are about 5 mm apart from HT7 points, were used as non-specific control acupuncture points. Most importantly, acupuncture at HT7, but not at LI5 significantly decreased relapse to cocaine-seeking, increased GABA release in the ventral tegmental area, and inhibited cocaine-induced decreases in GABA. Additionally, HT7 inhibition of cocaine-seeking behavior was blocked by microinfusion of the GABAB receptor antagonist 2-hydroxysaclofen into the ventral tegmental area. As suggested by many studies, chronic cocaine-induced depletion of dopamine in the nucleus accumbens may represent the mechanism, at least in part, that underlies the restlessness (dysphoria) and total loss in ability to feel pleasure (anhedonia) that accompanies cocaine withdrawal and might also contribute to the intense cocaine craving experienced by addicts. Accordingly, it would be interesting to assess whether acupuncture can reverse these neurobiological changes responsible for cocaine-induced negative affective states and deficits in brain reward. Acupuncture therapy has proven to be very effective for reducing nausea, pain, and drug abuse. However, very little is known about the basic mechanisms underlying the effectiveness of acupuncture in the treatment of drug addiction. Our results show evidence that may help us further understand the neurobiological underpinnings of acupuncture, and ultimately guide us in utilizing acupuncture to treat problems such as cocaine addiction.
Neuroscience 2013 (43rd annual meeting of the Society for Neuroscience)Exit