Comparison of brain activity between dopamine D2 receptor-knockout and wild mice in response to dopamine agonist and antagonist assessed by fMRI.
It has been reported that antipsychotic dopamine-D2-receptor (D2R) antagonists affected other neurotransmitter systems. In the present study, the effects of a D2R agonist, bromocriptine, and a D2R antagonist, spiperone, on brain activity were investigated using wild-type mice (WT) with intact D2Rs, and D2R-knockout mice (D2R-KO) lacking D2Rs by functional magnetic resonance imaging. In the WT, flow-weighted signal intensity significantly increased after administration of bromocriptine in the hippocampal formation. In contrast, signal intensity significantly decreased after administration of spiperone in the somatosensory-motor cortices, thalamus, anterior cingulate cortex, caudate-putamen, nucleus accumbens, hippocampal formation, and amygdala. In the D2R-KO, however, no significant changes were observed after administration of either bromocriptine or spiperone. The present results indicated that the D2R-KO lacked sensitivity to D2R agonist and antagonist in agreement with its genetic defects, which confirmed that the changes in brain activity in the WT after administration of either drug were mediated through D2Rs. These results suggest that antipsychotic D2R antagonists affect activity of the same brain regions of human patients through D2Rs, as observed in the present study. These changes in brain activity might be related to therapeutic efficacy as well as side effects of antipsychotic drugs on schizophrenic patients.
Molecular and Integrative Emotional Neuroscience, Graduate School of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama 930-0194, Japan.
Jun-Ichi
J
Kuriwaki
Hisao
H
Nishijo
Takashi
T
Kondoh
Teruko
T
Uwano
Kunio
K
Torii
Motoya
M
Katsuki
Taketoshi
T
Ono
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010100:Oxygen / Q000097:blood; D017448:Receptors, Dopamine D2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013997:Time Factors
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D010100:Oxygen