Title:Lithium Pharmacology and a Potential Role of Lithium on Methamphetamine Abuse and Dependence
VOLUME: 11
Author(s):Nobue Kitanaka, F. Scott Hall, George R. Uhl and Junichi Kitanaka*
Affiliation: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
Keywords:Lithium, methamphetamine abuse, phosphoinositide turnover, glycogen synthase kinase-3, nucleus accumbens.
Abstract: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.
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.
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.
