title: Treatment of the psychostimulant-sensitized animal model of schizophrenia.
abstract: Behavioral sensitization to psychostimulants in rodents is associated with the alteration of dopaminergic neurotransmission, and has been proposed as a useful model of schizophrenia due to its progressively intensifying, easily relapsing, and long-lasting features. Pharmacological treatments that reverse the established sensitization may have potential therapeutic values for schizophrenia. The present aim is to review pharmacological treatments that induce the reversal of established sensitization to psychostimulants. In addition, we discuss possible mechanisms for the reversal of sensitization. Reversal of sensitization is induced by chronic dopamine D1 receptor agonism, D2 or D1/D2 receptor agonism combined with mild N-methyl-D-aspartate (NMDA) receptor antagonism or serotonin (5-HT(2A) or 5-HT(3) ) receptor antagonism, 5-HT(1A) receptor agonism, and 5-HT(2A) or 5-HT(3) receptor antagonism. Chronic treatments with these drugs likely adjust altered dopaminergic neurotransmission in sensitized animals. Especially, chronic dopamine D1 receptor agonism, which may adjust mesolimbic hyperdopaminergic and mesocortical hypodopaminergic functions in sensitized animals, is an attractive therapeutic approach for schizophrenia.
authors.affiliation: Department of Pharmacology, Kurume University School of Medicine, Kurume, Fukuoka, Japan. shuto@med.kurume-u.ac.jp
authors.forename: Takahide
authors.initials: T
authors.lastname: Shuto
authors.forename: Akinori
authors.initials: A
authors.lastname: Nishi
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D004195:Disease Models, Animal; D004347:Drug Interactions; D006801:Humans; D011954:Receptors, Dopamine / Q000378:metabolism; D012559:Schizophrenia / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D011954:Receptors, Dopamine