TY - JOUR
T1 - Hippocampal GABAA antagonism reverses the novel object recognition deficit in sub-chronic phencyclidine-treated rats
AU - Neugebauer, Nichole M
AU - Miyauchi, Masanori
AU - Sato, Tatsuya
AU - Tadano, Jun
AU - Akal, Hanife
AU - Ardehali, Hossein
AU - Meltzer, Herbert Y.
PY - 2018/4/16
Y1 - 2018/4/16
N2 - 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.
AB - 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.
KW - GABA
KW - Hippocampus
KW - Novel object recognition
KW - Phencyclidine
KW - Prefrontal cortex
KW - Schizophrenia
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UR - http://www.scopus.com/inward/citedby.url?scp=85040234330&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2017.12.033
DO - 10.1016/j.bbr.2017.12.033
M3 - Article
C2 - 29289597
AN - SCOPUS:85040234330
VL - 342
SP - 11
EP - 18
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
ER -