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


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.
Mantsch
John R
JR
Department of Biomedical Sciences, Marquette University, Schroeder Health Complex, P.O. Box 1881, Milwaukee, WI 53201-1881, USA. john.mantsch@marquette.edu
Li
Shi-Jiang
SJ
Risinger
Robert
R
Awad
Sarah
S
Katz
Eric
E
Baker
David A
DA
Yang
Zheng
Z
D000818:Animals; D001600:Berberine Alkaloids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000517:prevention & control*; D003216:Conditioning, Operant / Q000187:drug effects; D031311:Corydalis; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors; D012008:Recurrence; D012646:Self Administration; D031607:Stephania; D013237:Stereoisomerism
D001600:Berberine Alkaloids; D004365:Drugs, Chinese Herbal; D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; C014215:tetrahydropalmatine; D003042:Cocaine