[D2-dopamine receptor upregulation and treatment response under neuroleptic therapy].
Animal and post mortem studies indicate that neuroleptic therapy may induce D2-dopamine receptor upregulation in the basal ganglia. To address this phenomenon in a clinical study, we investigated the D2-dopamine receptor binding in 15 DSM-III-R schizophrenics in the drug-naive state and three days after completion of a standardized neuroleptic therapy (benperidol 12-16 mg/d for 25 days) using single photon emission computed tomography (SPECT). SPECT scans were obtained 2 h after intravenous injection of 185 MBq 123I-IBZM. For analysis, basal ganglia to frontal cortex (BG/FC) ratios were calculated and the patient sample was subgrouped into patients with a favourable versus a poor treatment response. Neuroleptic treatment led to decreased BG/FC ratios in patients with a favourable response, but increased ratios in the poor responders (df = 1, F = 4.1, p = 0.06). Changes of BG/FC ratios were significantly correlated with extrapyramidal side effects, but not with neurological soft signs (NSS). Our findings indicate that neuroleptic therapy induces D2-dopamine receptor upregulation in a subgroup of patients characterized by poor treatment response and pronounced extrapyramidal side effects.
Schröder
J
J
Psychiatrische Universitätskliniken Heidelberg. johannes_schroeder@med.uni-heidelberg.de
Bubeck
B
B
Sauer
H
H
D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D001544:Benperidol / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D011569:Psychiatric Status Rating Scales; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis* / Q000187:drug effects; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon; D015854:Up-Regulation / Q000187:drug effects*
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D001544:Benperidol