Endogenously released dopamine inhibits the binding of dopaminergic PET and SPECT ligands in superfused rat striatal slices
✍ Scribed by Andrew N. Gifford; S. John Gatley; Charles R. Ashby Jr.
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 900 KB
- Volume
- 22
- Category
- Article
- ISSN
- 0887-4476
No coin nor oath required. For personal study only.
✦ Synopsis
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 present study we used a superfused brain slice preparation to examine the effect of synaptically released dopamine on the binding of some commonly used PET and SPECT radioligands under more controlled conditions than those present in vivo. The release of DA was evoked by electrical stimulation of striatal slices and the sensitivity of binding of the D, receptor ligand, [3H]SCH 23390, the Dz receptor ligands [3Hlraclopride and [lZ3I]epidepride, and the DA uptake transporter ligands, r3H]WIN 35,428 and [1231]RTI-55, to the frequency of stimulation examined. Most affected by stimulation was the specific binding of [3H]SCH 23390, which was fully inhibited at 2.5 Hz. This was followed by [3H]raclopride and [lZ3I]epidepride, respectively, the binding of the latter showing only a 50% reduction at the highest frequency of 10 Hz. [3H] WIN 35,428 and [1231]RTI-55 binding was unaffected by stimulation. The effects of stimulation on [3H]raclopride binding were prevented by reserpine pretreatment of the rat, when combined with inclusion of the dopamine synthesis inhibitor, a-methyl-p-tyrosine, in the superfusate medium. We conclude that, in brain slices, the binding of D, and D, receptor ligands but not that of DA uptake transporter ligands is readily inhibited by DA released into the synaptic cleft. Brain slices may prove to be a useful model system for the investigation of factors affecting competition between radioligand binding and endogenous neurotransmitters.