Paranoid schizophrenia may be caused by dopamine hyperactivity of CA1 hippocampus.
Explicit consolidation of memory, or fixation of declarative belief, appears to be physically represented in changes of synaptic conductances of neurons in the parietal-temporal-occipital association cortex (PTO) of the mammalian forebrain. This fixation of belief in PTO is postulated to be critically dependent on a diffuse reinforcement signal via the inferior temporal cortex (ITC) ultimately caused by an increased output of the CA1 pyramidal cells of hippocampus. Analogous to the reinforcing mechanisms of other forebrain systems, this updating of the connection weights of the neural nets in PTO by the output of the critical neurons in CA1 is directly related to concentrations of dopamine (DA). We propose that the delusions (i.e., unreasonable beliefs) of paranoid schizophrenia are caused by a hyperactivity of the same DA-sensitive CA1 neurons that are responsible for the fixation of normal beliefs. The dramatic reduction in delusions with administration of neuroleptics, as DA D2 blockers, in schizophrenics may thus be explained by their acting to ameliorate the hyperactivity of these CA1 DA D2 receptors.
New York University, Department of Psychology, NY 10003.
E E
EE
Krieckhaus
J W
JW
Donahoe
M A
MA
Morgan
D014150:Antipsychotic Agents / Q000627:therapeutic use; D001925:Brain Damage, Chronic / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D001931:Brain Mapping; D004298:Dopamine / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2; D012563:Schizophrenia, Paranoid / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D004298:Dopamine