Striatal dopamine receptors and transporters in monkeys with neonatal temporal limbic damage.
Developmental cortical damage has been implicated in the basic neurobiology of schizophrenia. Adult rhesus monkeys with neonatal temporal limbic damage show a stimulus-dependent disinhibition of subcortical dopamine (DA) release. We measured dopamine D2 receptors and transporters in vivo in rhesus monkeys with neonatal and adult mesial temporal limbic lesions and control monkeys to explore further the effects of this developmental lesion on striatal DA function. All monkeys were studied with [I-123]IBZM SPECT to assess the availability of striatal dopamine D2 receptors and with [I-123]beta-CIT SPECT to measure the availability of dopamine transporters in the striatum. IBZM binding was significantly reduced in monkeys with neonatal limbic lesions. No group difference in beta-CIT binding was found. The reduction in IBZM binding was significantly correlated with subcortical dopamine release after monoaminergic prefrontal stimulation as determined with in vivo microdialysis. Our findings imply specific interactions between age at lesion and the availability of DA transporter and receptors in non-human primates, and suggest that stimulus-dependent DA activity affects the expression of DA receptors.
Heinz
A
A
Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland 20892-1379, USA.
Saunders
R C
RC
Kolachana
B S
BS
Jones
D W
DW
Gorey
J G
JG
Bachevalier
J
J
Weinberger
D R
DR
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001549:Benzamides / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive / Q000502:physiology; D002352:Carrier Proteins / Q000032:analysis* / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D003287:Contrast Media; D003342:Corpus Striatum / Q000737:chemistry* / Q000000981:diagnostic imaging; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008032:Limbic System / Q000293:injuries*; D008253:Macaca mulatta; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D017551:Microdialysis; D009419:Nerve Tissue Proteins; D017397:Prefrontal Cortex / Q000378:metabolism; D011759:Pyrrolidines / Q000378:metabolism / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000032:analysis* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000032:analysis* / Q000378:metabolism; D013702:Temporal Lobe / Q000293:injuries*; D015899:Tomography, Emission-Computed, Single-Photon
D001549:Benzamides; D002352:Carrier Proteins; D003287:Contrast Media; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011759:Pyrrolidines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D003042:Cocaine; D004298:Dopamine