[Action of amygdala dopamine and effect of antipsychotics].
Although emotional dysfunction in patients with schizophrenia is thought to be associated with poorer outcomes in terms of overall quality of well-being, only a few basic studies have been done on the biochemical effect of antipsychotics on the fear response of a neurotransmitter (i.e. dopamine). To examine the reaction to emotional stress, conditioned fear stress has been developed as a form of psychological stress based on classical conditioning theory. Using this model, the amygdala was found to be one of the most potent modulators of the mechanisms responsible for the emotional memory system. Methamphetamine-induced sensitization (reverse tolerance phenomenon) in rats has been widely and successfully used as an animal model of stimulant-induced psychosis and schizophrenia in terms of the paranoid psychotic state and its vulnerability to relapse. Methamphetamine-sensitized animals show significantly higher extracellular dopamine release in the amygdala than unsensitized rats after exposure to a conditioned stimulus. This hypersensitivity of dopamine release is considered to be a biochemical marker of hypersensitivity and vulnerability to stress in psychosis. Aripiprazole and haloperidol equally suppressed the marked increase in extracellular dopamine levels in fear-conditioned rats, whereas haloperidol increased and aripiprazole decreased basal dopamine levels. The effect of antipsychotics attenuates the dopamine fear response in the amygdala, modulating basal dopamine level.
Oshibuchi
Hidehiro
H
Department of Psychiatry, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666 Japan. hoshibuchi@psy.twmu.ac.jp
Inada
Ken
K
Ishigooka
Jun
J
D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000068180:Aripiprazole; D002395:Catecholamines / Q000502:physiology; D003214:Conditioning, Classical / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D005239:Fear / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D012565:Schizophrenic Psychology; D013315:Stress, Psychological / Q000378:metabolism
D014150:Antipsychotic Agents; D002395:Catecholamines; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; D006220:Haloperidol; D004298:Dopamine