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Endogenously released dopamine inhibits the binding of dopaminergic PET and SPECT ligands in superfused rat striatal slices
Author(s) -
Gifford Andrew N.,
Gatley S. John,
Ashby Charles R.
Publication year - 1996
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199603)22:3<232::aid-syn5>3.0.co;2-d
Subject(s) - raclopride , dopaminergic , sch 23390 , chemistry , dopamine transporter , stimulation , dopamine , dopamine receptor d2 , in vivo , dopamine plasma membrane transport proteins , pharmacology , receptor , medicine , endocrinology , biochemistry , biology , microbiology and biotechnology
Pharmacologically induced changes in synaptic levels of dopamine (DA) have been found,in some studies, to affect the in vivo binding of dopaminergic radioligands. In the presentstudy we used a superfused brain slice preparation to examine the effect of synapticallyreleased dopamine on the binding of some commonly used PET and SPECT radioligandsunder more controlled conditions than those present in vivo. The release of DA was evokedby electrical stimulation of striatal slices and the sensitivity of binding of theD 1 receptor ligand, [ 3 H]SCH 23390, the D 2 receptor ligands [ 3 H]raclopride and [ 123 I]epidepride, and theDA uptake transporter ligands, [ 3 H]WIN 35,428 and[ 123 I]RTI‐55, to the frequency of stimulation examined. Most affected bystimulation was the specific binding of [ 3 H]SCH 23390, which was fullyinhibited at 2.5 Hz. This was followed by [ 3 H]raclopride and[ 123 I]epidepride, respectively, the binding of the latter showing only a 50%reduction at the highest frequency of 10 Hz. [ 3 H]WIN 35,428 and[ 123 I]RTI‐55 binding was unaffected by stimulation. The effects of stimulationon [ 3 H]raclopride binding were prevented by reserpine pretreatment of the rat,when combined with inclusion of the dopamine synthesis inhibitor, α‐methyl‐p‐tyrosine,in the superfusate medium. We conclude that, in brain slices, the binding of D 1 and D 2 receptor ligands but not that of DA uptake transporter ligands is readilyinhibited by DA released into the synaptic cleft. Brain slices may prove to be a useful modelsystem for the investigation of factors affecting competition between radioligand binding andendogenous neurotransmitters. © 1996 Wiley‐Liss, Inc.