Selective effects on prefrontal cortex serotonin by dopamine D3 receptor agonism: interaction with low-dose haloperidol.
1. Negative symptoms of schizophrenia are characterized by amotivation, anhedonia and anergia. These aspects of the symptom profile can be modeled by D3 agonism in animal behavioral models. 2. Serotonergic systems have been implicated in pathophysiologic substrates for this disorder; most notably, in deficit state schizophrenia, as newer 'atypical' neuroleptics which are especially efficacious for treating this syndrome antagonize central 5-HT2 receptors. 3. FC regions may also be important in chronic negative symptoms, as hypofrontality has been associated with these schizophrenic features. 4. The author examined effects of a behaviorally-active dose of the D3 agonist, 7OH, on 5-HT metabolism in FC, and the ability of a low-dose neuroleptic treatment to antagonize this biochemical effect. 5. Acute administration of 7OH induced a selective decrease of 5-HT turnover in the FC without affecting metabolism of this transmitter in more subcortical DA regions. 6. Hal, which has previously been demonstrated to antagonize electrophysiologic, biochemical and behavioral effects of 7OH, was without effect on agonist-induced decreases in 5-HT turnover. 7. The biochemical association between D3 agonism and reductions of FC 5-HT may be significant for pathophysiologic mechanisms of negative symptoms, and antagonism of this effect may differ for neuroleptics with varying efficacy in alleviating these symptoms.
Lynch
M R
MR
Research Service, Veterans Administration Medical Center, Syracuse, New York, USA.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D012701:Serotonin / Q000378:metabolism*
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D012701:Serotonin; D006220:Haloperidol