Individual and Combined Effects of Methamphetamine and Ketamine on Conditioned Place Preference and NR1 Receptor Phosphorylation in RatsXu D.D.a · Mo Z.X.a · Yung K.K.L.b · Yang Y.c · Leung A.W.N.d
aSchool of Chinese Medicine, Southern Medical University, Guangzhou, bDepartment of Biology, Hong Kong Baptist University, Hong Kong, SAR, cLaboratory of Cytology, Shandong University of Traditional Chinese Medicine, Jinan, and dSchool of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
Albert W.N. Leung, PhD
School of Chinese Medicine, The Chinese University of Hong Kong
Shatin, NT, Hong Kong, SAR (China)
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Methamphetamine (MA), a commonly abused psychostimulant, induces the drug dependence by enhancing the dopamine-mediated neurotransmission. Ketamine (KET) is a non-competitive N-methyl-D-aspartate receptor antagonist, which can be actually mixed with MA for polydrug abuse. In the present study, the individual and combined effects of KET (10 mg/kg, i.p.) and MA (1 mg/kg, i.p.) on conditioned place preference in rats were investigated. The alterations of serine 897 phosphorylations of NR1 receptors in the striatum and ventral tegmental area of after-conditioning rats were measured immunochemically. The results showed repeated administrations of MA, KET and their combination, at the doses studied, all could induce psychological dependences evaluated by conditioned place preference. KET was not able to suppress the MA-induced place preference. The modulations of NR1 phosphorylations in basal ganglia were partly responsible to place preference. Although the alterations induced by KET were not significant in most areas we studied, MA showed a significant increase in the ventral tegmental area but a marked decrease in caudate putamen and nucleus accumbens. Such alterations were much more significant when KET and MA were combined. These results have important implications for public awareness of harm with combined drug abuse. Further investigations toward the specific interaction of the two drugs are necessary.
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