Endogenous dopamine release after pharmacological challenges in Parkinson's disease

Abstract

Using (11)C-raclopride positron emission tomography after methamphetamine challenge, we have evaluated regional brain changes in synaptic dopamine (DA) levels in six volunteers and six advanced Parkinson's disease (PD) patients. The pharmacological challenge induced significant release of endogenous DA in putamen not only in the normal subjects, as reflected by a 25.2% reduction in (11)C-raclopride binding potential as compared with placebo, but also in the PD patients (6.8%). In individual PD patients, we found a correlation between putamen DA release and DA storage, as measured by (18)F-dopa uptake. Localization of significant changes in (11)C-raclopride binding after methamphetamine at a voxel level with statistical parametric mapping identified striatal and prefrontal DA release in both cohorts. Statistical comparisons between normal subjects and PD confirmed significantly reduced DA release in striatal areas in PD, but normal levels of prefrontal DA release. In conclusion, significant endogenous DA release can still be induced by pharmacological challenges in the putamen of advanced PD patients, and this release correlates with residual DA storage capacity. Our data also show that the capacity to release normal DA levels in prefrontal areas after a pharmacological challenge is preserved in severe stages of the disease.

Modulation of Amphetamine-Induced Dopamine Release by Group II Metabotropic Glutamate Receptor Agonist LY354740 in Non-Human Primates Studied with Positron Emission Tomography

“…The data set also documented the (Laruelle et al, 1997;Villemagne et al, 1999). The effect of methamphetamine on [ 11 C]raclopride in vivo binding is also significantly blunted in patients with Parkinson's disease (Piccini et al, 2003). Second, combined microdialysis and imaging experiments in primates demonstrated that, under conditions of dopamine transporter (DAT) blockade, the magnitude of the decrease in ligand binding was correlated with the magnitude of the increase in extracellular DA induced by the challenge (Breier et al, 1997;Laruelle et al, 1997;Tsukada et al, 1999a, b).…”

Neuroimaging in Parkinson's Disease

“…In contrast, [ 11 C]raclopride has a lower affinity, and its binding is accordingly affected by changes in the availability of synaptic DA [45,46]. This can be used to advantage to estimate DA release in response to a variety of pharmacological [47,48], physical [49][50][51], or behavioral [52][53][54] C-labeled PHNO [64] may be used to estimate changes in synaptic DA. Because of its relative selectivity, PHNO may also be useful for visualizing dopamine D3 receptors.…”

Amphetamine-Induced Displacement of [18F] Fallypride in Striatum and Extrastriatal Regions in Humans

“…Several brain imaging studies have investigated D-amphetamine (D-AMPH)-induced dopamine (DA) release in the striatum (Laruelle et al, 1995;Kegeles et al, 1999;Drevets et al, 2001;Singer et al, 2002;Piccini et al, 2003;Martinez et al, 2003;Volkow et al, 1994Volkow et al, , 2004. However, dopaminergic neurotransmission in cortex, thalamus, and limbic regions is believed to be significantly involved in psychosis, cognitive function, and psychostimulant drug abuse (Weinberger et al, 2001;Stevens, 1991;Kerwin and Murray, 1992;Goldman-Rakic, 1998;Yasuno et al, 2004;Koob and Le Moal, 2001).…”