Hippocampal GABAA antagonism reverses the novel object recognition deficit in sub-chronic phencyclidine-treated rats

Nichole M Neugebauer, Masanori Miyauchi, Tatsuya Sato, Jun Tadano, Hanife Akal, Hossein Ardehali, Herbert Y. Meltzer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 GABAA 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 GABAA agonist (muscimol) into the vHPC or mPFC and an antagonist (bicuculline) or a GABAA/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 GABAA γ2 in PFC and GABAA α5 and GABAA β1 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 GABAA receptor stimulation in vHPC, indicating that increased vHPC GABAA inhibition may contribute to the scPCP-induced NOR deficit in rats. These results also indicate that excessive GABAA receptor signalling in the vHPC has a deleterious effect on NOR in normal rats.

Original languageEnglish (US)
Pages (from-to)11-18
Number of pages8
JournalBehavioural Brain Research
Volume342
DOIs
StatePublished - Apr 16 2018

Keywords

  • GABA
  • Hippocampus
  • Novel object recognition
  • Phencyclidine
  • Prefrontal cortex
  • Schizophrenia

ASJC Scopus subject areas

  • Behavioral Neuroscience

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