K. Akiyama et al., METHAMPHETAMINE-INDUCED BEHAVIORAL SENSITIZATION AND ITS IMPLICATIONSFOR RELAPSE OF SCHIZOPHRENIA, Schizophrenia research, 12(3), 1994, pp. 251-257
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.