Alterations in prefrontal glutamatergic and noradrenergic systems following MK-801 administration in rats prenatally exposed to methylazoxymethanol at gestational day 17

Abstract

Given the importance of the mPFC in regulating the hyperlocomotor effect of NMDA antagonists, our results suggest that the prefrontal neurochemical alterations induced by MK-801 may sustain the exaggerated locomotor response in MAM-exposed rats.

N-Acetylcysteine– and MK-801–Induced Changes in Glutamate Levels Do Not Affect In Vivo Binding of Metabotropic Glutamate 5 Receptor Radioligand 11C-ABP688 in Rat Brain

“…1). In 1 animal, both a high-resolution, 9.4 T T2 MR image and a high-count (51.8 MBq) 11 C-ABP688 small-animal PET/CT image were obtained with a specially designed animal holder. This holder allowed the automated rigid registration of the anatomic MR and CT images and the subsequent coregistration of the PET image to the MR image.…”

“…The high-resolution MR image was then transformed to the Schiffer rat MR atlas available in PMOD v3.3 (PMOD brain normalization), which contains all of the delineated relevant brain VOIs. The 24 11 C-ABP688 baseline static images from the test-retest experiment (12 test and 12 retest images) were first normalized to the high-count PET image, and then the 25 images were iteratively averaged and registered (3 iterations). The average aligned 11 C-ABP688 image could then be transformed into the PMOD rat brain VOI space through the CT and MR imaging transforms.…”

“…At present, no imaging techniques are capable of measuring acute fluctuations in endogenous levels of glutamate in vivo, partly because of the lack of dedicated (radio)tracers. Recently, the visualization of acute fluctuations in endogenous glutamate levels was suggested (4) in a study performed in baboons with PET and the radioligand 11 C-ABP688 [3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-11 C-methyloxime], a highly selective allosteric antagonist of the metabotropic glutamate 5 receptor (mGluR5) (5). In that study (4), a significant decrease in 11 C-ABP688 binding relative to that at the baseline was observed in relevant brain regions after pharmacologic challenge with N-acetylcysteine (NAc).…”

“…In the present study, we attempted to confirm these findings in the rat brain by using small-animal PET and b-microprobes after pretreatments with NAc and MK-801. 11 C-ABP688 can exist in 2 stereoisomeric forms; the (E)-isomer (referred to here as 11 C-ABP688) is the most potent (5). To evaluate the in vivo stability of the 11 C-ABP688 tracer and possible isomerization, we performed an in vivo metabolite study during work-up and after an MK-801 challenge.…”

“…To evaluate the in vivo stability of the 11 C-ABP688 tracer and possible isomerization, we performed an in vivo metabolite study during work-up and after an MK-801 challenge. Further, to validate our small-animal PET setup with 11 C-ABP688, we performed both a test-retest study (n 5 12) and a blocking study (n 5 6) with unlabeled ABP688 by using a volume-of-interest (VOI) analysis in delineated structures that show specific 11 C-ABP688 binding: caudate putamen, frontal cortex, cerebral cortex, hippocampus, and thalamus (8,9). The cerebellum is a suitable reference region for calculating the nondisplaceable binding potential (BP ND ) of 11 C-ABP688 in rats and nonhuman primates (4,8), allowing for noninvasive quantification with the simplified reference tissue model (8,9).…”