Disruption of prefrontal cortical-hippocampal balance in a developmental model of schizophrenia: reversal by sulpiride.
The nucleus accumbens (NAc) receives converging inputs from the medial prefrontal cortex (mPFC) and the hippocampus which have competitive interactions in the NAc to influence motivational drive. We have previously shown altered synaptic plasticity in the hippocampal-NAc pathway in the methylazoxymethanol acetate (MAM) developmental model of schizophrenia in rodents that is dependent on cortical inputs. Thus, because mPFC-hippocampal balance is known to be partially altered in this model, we investigated potential pathological changes in the hippocampal influence over cortex-driven NAc spike activity. Here we show that the reciprocal interaction between the hippocampus and mPFC is absent in MAM animals but is able to be reinstated with administration of the antipsychotic drug, sulpiride. The lack of interaction between these structures in this model could explain the attentional deficits in schizophrenia patients and shed light onto their inability to focus on a single task.
Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA. belujon@pitt.edu
Pauline
P
Belujon
Mary H
MH
Patton
Anthony A
AA
Grace
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000633:toxicity; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013469:Sulpiride / Q000494:pharmacology / Q000627:therapeutic use*
D014150:Antipsychotic Agents; D008746:Methylazoxymethanol Acetate; D013469:Sulpiride