title: Levo-tetrahydropalmatine, a natural, mixed dopamine receptor antagonist, inhibits methamphetamine self-administration and methamphetamine-induced reinstatement.
abstract: Despite the high prevalence of methamphetamine (METH) use, no FDA-approved pharmacological treatment is currently available for individuals with a METH addiction. Levo-tetrahydropalmatine (l-THP) is an alkaloid substance derived from corydalis and stephania that has been used in traditional Asian medicine for its analgesic, sedative and hypnotic properties. Previous pharmacological studies of l-THP indicated that it not only binds to D1 and D2 receptors but also has a low affinity for D3 receptors and may function as an antagonist. The unique pharmacological profile of l-THP suggests that it may have potential therapeutic effects on drug addiction; however, the effects of l-THP in individuals with METH addictions are largely unknown. In this study, we investigated the effects of l-THP on METH self-administration and METH-induced reinstatement. In our experiments, l-THP (1.25, 2.50 and 5.00 mg/kg, i.p.) decreased METH self-administration under the fixed-ratio 1 schedule. l-THP (2.50 and 5.00 mg/kg, i.p) also prevented the METH-induced reinstatement of METH-seeking behaviors. Interestingly, l-THP (1.25 and 2.50mg/kg, i.p) did not affect locomotor activity following METH injection (1mg/kg) suggesting that the observed effects of l-THP (2.50mg/kg) on METH-induced reinstatement were not due to motor impairments. Thus, l-THP (a natural, mixed dopamine (DA) receptor antagonist) attenuates METH self-administration and METH-induced reinstatement.
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan 430056, China.
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Gong
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan 430056, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yue
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan 430056, China.
authors.forename: Baomiao
authors.initials: B
authors.lastname: Ma
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan 430056, China.
authors.forename: Junqiao
authors.initials: J
authors.lastname: Xing
authors.affiliation: Drug Prevention and Education Center, Hubei Public Security Bureau, Wuhan 430070, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Gan
authors.affiliation: Drug Prevention and Education Center, Hubei Public Security Bureau, Wuhan 430070, China.
authors.forename: Daisong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan 430056, China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201213, China.
authors.forename: Guozhang
authors.initials: G
authors.lastname: Jin
authors.affiliation: Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan 430056, China. Electronic address: licy.whibs@aliyun.com.
authors.forename: Chaoying
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D001600:Berberine Alkaloids / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration
chemical_list: D001600:Berberine Alkaloids; D018492:Dopamine Antagonists; C014215:tetrahydropalmatine; D008694:Methamphetamine
keywords: Antagonist; Dopamine; Levo-tetrahydropalmatine; Methamphetamine; Reinstatement; Self-administration