Cebus apella, a nonhuman primate highly susceptible to neuroleptic side effects, carries the GLY9 dopamine receptor D3 associated with tardive dyskinesia in humans.
Tardive dyskinesia (TD) is a severe side effect of traditional neuroleptics affecting a considerable number of schizophrenic patients. Accumulating evidence suggests the existence of a genetic disposition to TD and other extra pyramidal symptoms (EPS) most strongly linked to a ser/gly polymorphism in position 9 of the D3 dopamine receptor gene (DRD3). The Cebus apella monkey is the favored animal model to study TD and other EPS because of its high susceptibility to side effects of neuroleptics. We therefore determined the sequence of the DRD3 gene in this species and compared it with that of humans. We found that the highly TD susceptible C. apella monkey (n=21) carries the gly9/gly9 DRD3 genotype that has been associated with TD in humans. Contrarily, C. apella did not carry the ser23 5HT2C allele that has been reported to increase TD susceptibility in humans.
Research Institute of Biological Psychiatry, Sct. Hans Hospital, DK-4000 Roskilde, Denmark. thomas.werge@shh.hosp.dk
T
T
Werge
Z
Z
Elbaek
M B
MB
Andersen
J A
JA
Lundbaek
H B
HB
Rasmussen
D019943:Amino Acid Substitution; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D002428:Cebus; D004409:Dyskinesia, Drug-Induced / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014150:Antipsychotic Agents; C493593:DRD3 protein, human; D044405:Receptor, Serotonin, 5-HT2C; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3