Compound 42c-R exhibited dose-dependent inhibition of [125I]-CRF binding in the frontal cortex (5 and 10 mg/kg, p.o). as well as suppression of locomotor activation induced by intracerebroventricular administration of CRF in rats (10 mg/kg, p.o).
Third, we found a reduction of [11C]CHIBA-1001 binding in the frontal cortex of the monkey brain after subchronic administration of PCP.
In the same study, BM also reversed the (a) depletion of acetylcholine, (b) reduction in choline acetyltransferase activity, and (c) decrease in muscarinic cholinergic receptor binding in the frontal cortex and hippocampus [ 47].
Interestingly, deprivation of only one night of sleep increases adenosine A1 receptor binding in the frontal cortex in human (Elmenhorst et al. 2007) and in cortical regions in rat (Elmenhorst et al. 2009).
In brief, studies of postmortem brain tissue have reported reduced nAChR binding in the frontal and parietal cortices (comparing 7 cases with 10 controls), reduced M1-muscarinic receptor binding in the parietal cortex (comparing 5 cases with 5 controls), and increased concentration of brain-derived neurotrophic factor (BDNF) (comparing 5 cases with 5 controls) (Deutsch et al. 2010).
We obtained arterial blood samples for kinetic data analysis and found that the compound had a differential distribution in brain regions, with the highest binding potentials in the frontal and temporal cortices, intermediate binding potential in the thalamus, and low binding potentials in the striatum, hypothalamus, and brainstem.
The selective δ-OR antagonist [C-methyl]naltrindole (C-MeNal) showed a high binding availability in the frontal cortex and putamen, lower levels in thalamus and an absence of specific binding in the human cerebellum (Smith et al., 1999).
Lower dopamine transporter binding has been associated with decreased initiative [ 55], whereas lower cholinergic receptor binding in the left frontal cortex has been reported to be associated with motor and mood changes of apathy [ 56].
The regional distribution of [C]AZD2995 radioactivity in AD patients was similar to that found for other amyloid-β radioligands showing high binding in the parietal, frontal, parietotemporal and posterior cingulate cortices [ 5, 14, 30].
Interestingly, the binding of [11C]CHIBA-1001 in the frontal cortex of the monkey brain was significantly decreased by subchronic administration of the N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (0.3 mg/kg, twice a day for 13 days); which is a non-human primate model of schizophrenia.
Given that A2AR distribution is heterogeneous, with only a very small amount of extrastriatal-specific binding, either the frontal cortex in the rat [3], the cerebellum in the monkey [10],[11], or centrum semiovale [7] or cerebral cortex [8],[9] in human, was used as a reference region to estimate non-displaceable binding of 11C-TMSX.
