Uncoupling the dopamine D1-D2 receptor complex exerts antidepressant-like effects.
We report that coupling between dopamine D1 and D2 receptors was markedly increased in postmortem brain of subjects suffering from major depression. Biochemical analyses revealed that D1 and D2 receptors form heterodimers via a direct protein-protein interaction. Administration of an interfering peptide that disrupts the D1-D2 receptor complex substantially reduced immobility in the forced swim test (FST) without affecting locomotor activity, and decreased escape failures in learned helplessness tests in rats.
Department of Neuroscience, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Lin
L
Pei
Shupeng
S
Li
Min
M
Wang
Mustansir
M
Diwan
Hymie
H
Anisman
Paul J
PJ
Fletcher
José N
JN
Nobrega
Fang
F
Liu
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003863:Depression / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D019281:Dimerization; D004924:Escape Reaction / Q000187:drug effects; D006380:Helplessness, Learned; D006801:Humans; D047468:Immunoprecipitation; D008124:Locomotion / Q000187:drug effects; D046912:Multiprotein Complexes / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D046912:Multiprotein Complexes; D027361:Organic Anion Transporters; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011993:Recombinant Fusion Proteins; C487007:gonad-specific transporter-1, rat; D054322:tat Gene Products, Human Immunodeficiency Virus