Mr. Lynch, SELECTIVE EFFECTS ON PREFRONTAL CORTEX SEROTONIN BY DOPAMINE D3 RECEPTOR AGONISM - INTERACTION WITH LOW-DOSE HALOPERIDOL, Progress in neuro-psychopharmacology & biological psychiatry, 21(7), 1997, pp. 1141-1153
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.