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Levo-tetrahydropalmatine attenuates cocaine self-administration and cocaine-induced reinstatement in rats

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Abstract

Rationale

Levo-tetrahydropalmatine (l-THP) is an alkaloid constituent of plants from the botanical genera Corydalis and Stephania and is contained in many traditional Chinese herbal preparations. In addition to its low-affinity antagonism of D2 dopamine (DA) receptors, we report that l-THP functions as a higher-affinity antagonist at D1 DA receptors and interacts with D3 DA receptors, suggesting that it may be effective for the treatment of drug addiction. Accordingly, l-THP has been reported to reduce heroin craving and relapse in recovering addicts.

Objective

This study investigated the effects of l-THP (3.75, 7.5, and 15.0 mg/kg, i.p.) on cocaine self-administration (SA) and cocaine-induced reinstatement.

Materials and methods

Rats were trained to self-administer cocaine and food by pressing separate response levers during sessions consisting of a multiple schedule of alternating 30-min FR4 cocaine and 15-min FR4 food reinforcement. During the cocaine components of each session, the available cocaine dose varied such that rats had access to low and high dose ranges in varying sequence on alternating days. After SA, cocaine-reinforced responding was extinguished, and effects of l-THP on cocaine-induced reinstatement (10 mg/kg, i.p.) were examined.

Results

l-THP produced a rightward and downward shift in the dose–response curve for cocaine SA and attenuated cocaine-induced reinstatement. l-THP also reduced food-reinforced responding and locomotor activity. However, reductions in cocaine SA were found at doses that failed to alter food-reinforced responding, and significant effects were not observed on food responding during reinstatement.

Conclusions

These findings suggest that l-THP is potentially useful for treating cocaine addiction.

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Acknowledgment

This work was supported by NIH grant numbers DA15758 to JRM and EB01820 to SJL and by Chinese Ministry of Science and Technology grant number 2003CB51540 to ZY. The authors would like to thank Joseph Serge and Michael Hoks for their technical assistance.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Marquette University, Schroeder Health Complex, P.O. Box 1881, Milwaukee, WI, 53201-1881, USA

    John R. Mantsch, Sarah Awad, Eric Katz & David A. Baker

  2. Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA

    Shi-Jiang Li

  3. Department of Psychiatry, Medical College of Wisconsin, Milwaukee, WI, USA

    Robert Risinger

  4. Beijing Institute of Basic Medical Sciences, Beijing, China

    Zheng Yang

Authors
  1. John R. Mantsch
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  2. Shi-Jiang Li
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  4. Sarah Awad
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  5. Eric Katz
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  6. David A. Baker
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  7. Zheng Yang
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Correspondence to John R. Mantsch.

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Mantsch, J.R., Li, SJ., Risinger, R. et al. Levo-tetrahydropalmatine attenuates cocaine self-administration and cocaine-induced reinstatement in rats. Psychopharmacology 192, 581–591 (2007). https://doi.org/10.1007/s00213-007-0754-7

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  • DOI: https://doi.org/10.1007/s00213-007-0754-7

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