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  • Addiction, Drugs
  • 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.