METHAMPHETAMINE-INDUCED BEHAVIORAL SENSITIZATION AND ITS IMPLICATIONSFOR RELAPSE OF SCHIZOPHRENIA

Vulnerability to relapse is a central issue in the biology of schizoph renia. The common neural mechanisms underlying such vulnerability can be studied using the experimental model of behavioral sensitization in duced by repeated administration of low doses of methamphetamine (MAP) to rodents. This review summarizes a series of behavioral and neuroch emical studies on MAP-induced behavioral sensitization from the viewpo int that the mechanisms involved in initiation (or development) of psy chotic symptoms and their expression differ. The initiation of behavio ral sensitization to MAP in rats requires stimulation of dopaminergic neurons, and can be blocked by SCH 23390 (a dopamine D1-receptor antag onist) 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 en hanced. Second, the behavioral responses to dopamine D2- and sigma-rec eptor agonists are augmented. A third form involves changes indicative of transsynaptic neural circuits, such as increased numbers of D1 rec eptors in the substantia nigra pars reticulata, enhanced electrophysio logical responses to D1 receptor activation, the putative role of exci tatory amino acid receptors and interchangeability of MAP and stress. Although MAP-induced behavioral sensitization in rodents serves as a u seful animal model, the elucidation of the mechanisms involved in the vulnerability of patients with schizophrenia to relapse of psychotic e pisodes requires further study.