Nobue Kitanaka, Frank Scott Hall, George Richard Uhl and Junichi Kitanaka* Pages 85 - 91 ( 7 )
<P>Background: The effectiveness of lithium salts in neuropsychiatric disorders such as bipolar disorder, Alzheimer’s disease, and treatment-resistant depression has been documented in an extensive scientific literature. Lithium inhibits inositol monophosphatase, inositol polyphosphate 1- phosphatase, and glycogen synthase kinase-3 and decreases expression level of tryptophan hydroxylase 2, conceivably underlying the mood stabilizing effects of lithium, as well as procognitive and neuroprotective effects. However, the exact molecular mechanisms of action of lithium on mood stabilizing and pro-cognitive effects in humans are still largely unknown. </P><P> Objective: On the basis of the known aspects of lithium pharmacology, this review will discuss the possible mechanisms underlying the therapeutic effects of lithium on positive symptoms of methamphetamine abuse and dependence. </P><P> Conclusion: It is possible that lithium treatment reduces the amount of newly synthesized phosphatidylinositol, potentially preventing or reversing neuroadaptations contributing to behavioral sensitization induced by methamphetamine. In addition, it is suggested that exposure to repeated doses of methamphetamine induces hyperactivation of glycogen synthase kinase-3β in the nucleus accumbens and in dorsal hippocampus, resulting in a long-term alterations in synaptic plasticity underlying behavioral sensitization as well as other behavioral deficits in memory-related behavior. Therefore it is clear that glycogen synthase kinase-3β inhibitors can be considered as a potential candidate for the treatment of methamphetamine abuse and dependence.</P>
Lithium, methamphetamine abuse, phosphoinositide turnover, glycogen synthase kinase-3, nucleus accumbens, neuropsychiatric disorders.
Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501, Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, Ohio 43614, Neurology and Research Services, New Mexico VA Healthcare System, Albuquerque, New Mexico 87108, Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501