Effects of endogenous neurotransmitters on the in vivo binding of dopamine and 5-HT radiotracers in mice.

Several studies have indicated that the in vivo binding of D(2) receptor positron emission tomography radiotracers can, under some conditions, be influenced by competition with endogenous dopamine. The present study was undertaken to compare the extent to which the in vivo binding in mice of radiotracers to other amine neuroreceptors, namely D(1), 5-HT(2A) and 5-HT(1A) receptors, can also be modulated by neurotransmitter competition. For dopamine radiotracers we examined [3H]raclopride as a D(2) radiotracer and [3H]A69024 as a D(1) radiotracer. Striatal binding of both radiotracers was substantially reduced by administration of the dopamine releaser, amphetamine, although only at a high dose. [3H]raclopride was decreased more than [3H]A69024. Dopamine depletion with 4-hydroxybutyrate strongly increased [3H]raclopride binding but failed to increase [3H]A69024 binding. For 5-HT radiotracers we examined [3H]N-methylspiperone as a 5-HT(2A) radiotracer and [3H]WAY 100635 as a 5-HT(1A) radiotracer. Cortical binding of both radiotracers was unaffected by the 5-HT releaser, p-chloroamphetamine. [3H]WAY 100635 binding was additionally unaffected by 5-HT release with fenfluramine and by 5-HT depletion with p-chlorophenylalanine. In conclusion, of the four radiotracers examined, [3H]raclopride binding to D(2) receptors had greatest sensitivity to changes in endogenous neurotransmitter levels. [3H]A69024 binding to D(1) receptors was affected only by neurotransmitter increases. [3H]N-methylspiperone binding to 5-HT(2A) receptors and [3H]WAY 100635 binding to 5-HT(1A) receptors appeared insensitive to changes in neurotransmitter levels.