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 m odeled by D3 agonism in animal behavioral models. 2. Serotonergic syst ems have been implicated in pathophysiologic substrates for this disor der; most notably, in deficit state schizophrenia, as newer 'atypical' neuroleptics which are especially efficacious for treating this syndr ome antagonize central 5-HT2 receptors. 3. FC regions may also be impo rtant in chronic negative symptoms, as hypofrontality has been associa ted with these schizophrenic features. 4. The author examined effects of a behaviorally-active dose of the D3 agonist, 70H, on 5-HT metaboli sm in FC, and the ability of a low-dose neuroleptic treatment to antag onize this biochemical effect. 5. Acute administration of 70H induced a selective decrease of 5-HT turnover in the FC without affecting meta bolism of this transmitter in more subcortical DA regions. 6. Hal, whi ch has previously been demonstrated to antagonize electrophysiologic, biochemical and behavioral effects of 70H, was without effect on agoni st-induced decreases in 5-HT turnover. 7. The biochemical association between D3 agonism and reductions of FC 5-HT may be significant for pa thophysiologic mechanisms of negative symptoms, and antagonism of this effect may differ for neuroleptics with varying efficacy in alleviati ng these symptoms.