Journal
DRUG AND ALCOHOL DEPENDENCE
Volume 116, Issue 1-3, Pages 72-79Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.drugalcdep.2010.11.023
Keywords
Relapse; Dopamine; THP; Craving; Cocaine; Reinstatement
Categories
Funding
- National Institute on Drug Abuse (NIDA) [DA015758, DA017328]
- National Center for Complementary and Alternative Medicine (NCCAM) [AT004736]
- NIH
- State of Wisconsin Biotechnology Alliance
- National Alliance for Research on Schizophrenia and Addiction
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Cocaine addiction is characterized by a persistently heightened susceptibility to drug relapse. For this reason, the identification of medications that prevent drug relapse is a critical goal of drug abuse research. Drug re-exposure, the onset of stressful life events, and exposure to cues previously associated with drug use have been identified as determinants of relapse in humans and have been found to reinstate extinguished cocaine seeking in rats. This study examined the effects of acute oral (gavage) administration of levo-tetrahydropalmatine (l-THP), a tetrahydroprotoberberine isoquinoline with a pharmacological profile that includes antagonism of D1, D2 and D3 dopamine receptors, on the reinstatement of extinguished cocaine seeking by a cocaine challenge (10 mg/kg, ip), a stressor (uncontrollable electric footshock [EFS]) or response-contingent exposure to a stimulus (tone and light complex) previously associated with drug delivery in male Sprague-Dawley rats. Extinguished drug seeking was reinstated by ip cocaine, EFS, or response-contingent presentation of drug-associated cues in vehicle-pretreated rats following extinction of iv cocaine self-adminisration. Oral administration of either 3.0 or 10.0 mg/kg l-THP 1 h prior to reinstatement testing significantly attenuated reinstatement by each of the stimuli. Food-reinforced responding and baseline post-extinction responding were significantly attenuated at the 10.0, but not the 3.0 mg/kg, l-THP dose, indicating that the effects of 3 mg/kg l-THP on reinstatement were likely independent of non-specific motor impairment. These findings further suggest that l-THP may have utility for the treatment of cocaine addiction. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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