Methamphetamine-induced behavioral sensitization and its implications for relapse of schizophrenia.
Vulnerability to relapse is a central issue in the biology of schizophrenia. The common neural mechanisms underlying such vulnerability can be studied using the experimental model of behavioral sensitization induced by repeated administration of low doses of methamphetamine (MAP) to rodents. This review summarizes a series of behavioral and neurochemical studies on MAP-induced behavioral sensitization from the viewpoint that the mechanisms involved in initiation (or development) of psychotic symptoms and their expression differ. The initiation of behavioral sensitization to MAP in rats requires stimulation of dopaminergic neurons, and can be blocked by SCH 23390 (a dopamine D1-receptor antagonist) and BMY 14802 (a sigma-receptor antagonist). The expression of behavioral sensitization induced by subchronic MAP pretreatment takes several forms. First, dopamine release from the cerebral dopaminergic neuron terminal containing areas in response to either to rechallenge with MAP or cocaine, or evoked by intrastriatal ouabain infusion is enhanced. Second, the behavioral responses to dopamine D2- and sigma-receptor agonists are augmented. A third form involves changes indicative of transsynaptic neural circuits, such as increased numbers of D1 receptors in the substantia nigra pars reticulata, enhanced electrophysiological responses to D1 receptor activation, the putative role of excitatory amino acid receptors and interchangeability of MAP and stress. Although MAP-induced behavioral sensitization in rodents serves as a useful animal model, the elucidation of the mechanisms involved in the vulnerability of patients with schizophrenia to relapse of psychotic episodes requires further study.
Akiyama
K
K
Department of Neuropsychiatry, Okayama University Medical School, Japan.
Kanzaki
A
A
Tsuchida
K
K
Ujike
H
H
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000096:biosynthesis*; D006801:Humans; D008694:Methamphetamine / Q000494:pharmacology*; D008954:Models, Biological; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects; D017480:Receptors, sigma / Q000187:drug effects; D012008:Recurrence; D012559:Schizophrenia / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D017447:Receptors, Dopamine D1; D017480:Receptors, sigma; D008694:Methamphetamine; D004298:Dopamine