Hippocampal GABA A antagonism reverses the novel object recognition deficit in sub-chronic phencyclidine-treated rats
Abstract
Background Abnormalities in prefrontal cortical and hippocampal GABAergic function are postulated to be major causes of the cognitive impairment associated with schizophrenia (CIAS). There are conflicting views on whether diminished or enhanced GABAergic activity contributes to the deficit in short-term novel object recognition (NOR) in the sub-chronic phencyclidine (scPCP) rodent model of CIAS. This study assessed the role of GABA A signaling in the medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC) in NOR in saline (scSAL)- and scPCP-treated rats.Methods The effects of local administration of a GABA A agonist (muscimol) into the vHPC or mPFC and an antagonist (bicuculline) or a GABA A/benzodiazepine partial agonist (bretazenil) into the vHPC on NOR in scSAL and scPCP-treated rats were determined.Results In scSAL-treated rats, injection of muscimol into the vHPC, but not mPFC, induced a deficit in NOR. The scPCP-induced NOR deficit was significantly reversed by intra-vHPC bicuculline, while intra-vHPC bretazenil produced a non-significant trend for reversal (p = .06). scPCP treatment increased mRNA expression of GABA A γ 2 in PFC and GABA A α 5 and GABA A β 1 in the HPC. However, GABA concentration in the PFC or HPC was not altered.Conclusions These findings indicate that the scPCP-induced NOR deficit can be rescued by reducing GABA A receptor stimulation in vHPC, indicating that increased vHPC GABA A inhibition may contribute to the scPCP-induced NOR deficit in rats. These results also indicate that excessive GABA A receptor signalling in the vHPC has a deleterious effect on NOR in normal rats.
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Pharmacological inhibition of the mPFC with muscimol before the sample trial has no effect in the NOP test.
“Pharmacological inhibition of the mPFC with muscimol, a GABAA-R agonist, also had no effect in the NOP test when infused before the sample trial (Neugebauer et al., 2018; Pezze et al., 2017).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Neugebauer et al., 2018
The ventral hippocampus is involved in NOP memory, as muscimol infusions led to NOP deficits.
“The ventral hippocampus is also involved in NOP memory, as muscimol infusions led to NOP deficits (Neugebauer et al., 2018), albeit this was not supported by a lesion study (Broadbent et al., 2004).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Neugebauer et al., 2018
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BindingDB (2023) · UC San Diego · doi:10.7270/q2dv1q01
- Authors
- Neugebauer, N. M., Miyauchi, M., Sato, T., Tadano, J., Akal, H., Ardehali, H., & Meltzer, H. Y.
- Affiliations
- Northwestern University (US)
- Sumitomo Dainippon Pharma (Japan) (JP)
- Corresponding author
- Meltzer, Herbert Y.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 342
- Pages
- 11-18
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2779889570
- Cited by
- 7
- References
- 70
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- GABAA receptor, hippocampus, medial prefrontal cortex, novel object recognition, schizophrenia, cognitive impairment, muscimol, bicuculline, bretazenil, GABAergic inhibition
- MeSH terms
- Animals, Attention, Bicuculline, Female, Hippocampus, Muscimol, Phencyclidine, Receptors, GABA-A, Prefrontal Cortex, Rats, Long-Evans, Recognition, Psychology, Models, Animal, Rats, GABA-A Receptor Agonists, GABA-A Receptor Antagonists, Cognitive Dysfunction
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