2021
DOI: 10.1038/s41386-021-01213-0
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GABAA and NMDA receptor density alterations and their behavioral correlates in the gestational methylazoxymethanol acetate model for schizophrenia

Abstract: Hippocampal hyperactivity driven by GABAergic interneuron deficits and NMDA receptor hypofunction is associated with the hyperdopaminergic state often observed in schizophrenia. Furthermore, previous research in the methylazoxymethanol acetate (MAM) rat model has demonstrated that repeated peripubertal diazepam administration can prevent the emergence of adult hippocampal hyperactivity, dopamine-system hyperactivity, and associated psychosis-relevant behaviors. Here, we sought to characterize hippocampal GABAA… Show more

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Cited by 10 publications
(13 citation statements)
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“…Other rodent models used to study psychosis display deficits in hippocampal α5-GABA A R expression ( Kiemes et al, 2021 ). To determine whether inescapable shock altered total levels of α5-GABA A Rs in the vHipp, we performed western-blot analysis in control and shocked rats and demonstrated that IS did not significantly alter α5-GABA A Rs levels in the vHipp ( Fig.…”
Section: Resultsmentioning
confidence: 99%
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“…Other rodent models used to study psychosis display deficits in hippocampal α5-GABA A R expression ( Kiemes et al, 2021 ). To determine whether inescapable shock altered total levels of α5-GABA A Rs in the vHipp, we performed western-blot analysis in control and shocked rats and demonstrated that IS did not significantly alter α5-GABA A Rs levels in the vHipp ( Fig.…”
Section: Resultsmentioning
confidence: 99%
“…A more parsimonious explanation for these results is that receptor overexpression does not address the underlying deficits observed in PTSD. In the methylazoxymethanol acetate (MAM) model used to study psychosis, rats have been shown to have reduced number of interneurons ( Lodge et al, 2009 ) as well as decreased α5-GABA A R density in the hippocampus ( Kiemes et al, 2021 ), which may account for why α5 overexpression successfully treated dopamine system dysfunction in MAM rats ( Donegan et al, 2019 ). However, aberrant hippocampal function in PTSD may not be due to decreased GABARs ( Gilbertson et al, 2002 ; Villarreal et al, 2002 ; Bremner et al, 2003 ; Girgenti et al, 2021 ).…”
Section: Discussionmentioning
confidence: 99%
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“…Frozen brains were coronally cryosectioned at 20 µm and mounted onto glass slides, then dried on a hotplate. Quantitative autoradiography was performed as previously described 65 , 66 using radioligands [ 3 H]Ro15-4513, [ 3 H]flumazenil, and [ 3 H]UCB-J. All slides were immersed in Tris buffer (50 mM) for 20 min prior to incubation with radioligands for specific or nonspecific binding, and incubation was followed by 2 washes in Tris buffer for 2 min each, and a rinse in dH 2 O, before overnight air-drying.…”
Section: Methodsmentioning
confidence: 99%
“…Frozen brains were coronally cryosectioned at 20µm and mounted onto glass slides, then dried on a hotplate. Quantitative autoradiography was performed as previously described 74,75 using radioligands [ 3 H]Ro15-4513, [ 3 H]flumazenil and [ 3 H]UCB-J. All slides were soaked in Tris buffer (50mM) for 20 minutes prior to incubation with radioligands for specific or non-specific binding, and this was followed by two washes in Tris buffer for 2 minutes each, and a rinse in dH 2 O, before overnight air-drying.…”
Section: Methodsmentioning
confidence: 99%