PMID- 38256109
OWN - NLM
STAT- MEDLINE
DCOM- 20240124
LR  - 20240202
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 25
IP  - 2
DP  - 2024 Jan 14
TI  - Differential Effects of Aripiprazole on Electroencephalography-Recorded 
      Gamma-Band Auditory Steady-State Response, Spontaneous Gamma Oscillations and 
      Behavior in a Schizophrenia Rat Model.
LID - 10.3390/ijms25021035 [doi]
LID - 1035
AB  - The available antipsychotics for schizophrenia (SZ) only reduce positive symptoms 
      and do not significantly modify SZ neurobiology. This has raised the question of 
      the robustness and translational value of methods employed during drug 
      development. Electroencephalography (EEG)-based measures like evoked and 
      spontaneous gamma oscillations are considered robust translational biomarkers as 
      they can be recorded in both patients and animal models to probe a key mechanism 
      underlying all SZ symptoms: the excitation/inhibition imbalance mediated by 
      N-methyl-D-aspartate receptor (NMDAr) hypofunction. Understanding the effects of 
      commercialized atypical antipsychotics on such measures could therefore 
      contribute to developing better therapies for SZ. Yet, the effects of such drugs 
      on these EEG readouts are unknown. Here, we studied the effect of the atypical 
      antipsychotic aripiprazole on the gamma-band auditory steady-state response 
      (ASSR), spontaneous gamma oscillations and behavioral features in a SZ rat model 
      induced by the NMDAr antagonist MK-801. Interestingly, we found that aripiprazole 
      could not normalize MK-801-induced abnormalities in ASSR, spontaneous gamma 
      oscillations or social interaction while it still improved MK-801-induced 
      hyperactivity. Suggesting that aripiprazole is unable to normalize 
      electrophysiological features underlying SZ symptoms, our results might explain 
      aripiprazole's inefficacy towards the social interaction deficit in our model but 
      also its limited efficacy against social symptoms in patients.
FAU - Adraoui, Florian W
AU  - Adraoui FW
AUID- ORCID: 0009-0004-0563-8932
AD  - Biotrial, Non-Clinical Pharmacology Department, 7-9 Rue Jean-Louis Bertrand, 
      35000 Rennes, France.
FAU - Hettak, Kenza
AU  - Hettak K
AD  - Biotrial, Non-Clinical Pharmacology Department, 7-9 Rue Jean-Louis Bertrand, 
      35000 Rennes, France.
FAU - Viardot, Geoffrey
AU  - Viardot G
AD  - Biotrial, Neuroscience Department, 6 Avenue de Bruxelles, 68350 
      Brunstatt-Didenheim, France.
FAU - Alix, Magali
AU  - Alix M
AD  - Biotrial, Non-Clinical Pharmacology Department, 7-9 Rue Jean-Louis Bertrand, 
      35000 Rennes, France.
FAU - Guiffard, Sabrina
AU  - Guiffard S
AD  - Biotrial, Non-Clinical Pharmacology Department, 7-9 Rue Jean-Louis Bertrand, 
      35000 Rennes, France.
FAU - Meot, Benoit
AU  - Meot B
AD  - Biotrial, Non-Clinical Pharmacology Department, 7-9 Rue Jean-Louis Bertrand, 
      35000 Rennes, France.
FAU - L'Hostis, Philippe
AU  - L'Hostis P
AD  - Biotrial, Neuroscience Department, 7-9 Rue Jean-Louis Bertrand, 35000 Rennes, 
      France.
FAU - Maurin, Anne
AU  - Maurin A
AD  - Biotrial, Non-Clinical Pharmacology Department, 7-9 Rue Jean-Louis Bertrand, 
      35000 Rennes, France.
FAU - Delpy, Eric
AU  - Delpy E
AD  - Biotrial, Non-Clinical Pharmacology Department, 7-9 Rue Jean-Louis Bertrand, 
      35000 Rennes, France.
FAU - Drieu La Rochelle, Christophe
AU  - Drieu La Rochelle C
AD  - Biotrial, Non-Clinical Pharmacology Department, 7-9 Rue Jean-Louis Bertrand, 
      35000 Rennes, France.
FAU - Carvalho, Kevin
AU  - Carvalho K
AD  - Biotrial, Non-Clinical Pharmacology Department, 7-9 Rue Jean-Louis Bertrand, 
      35000 Rennes, France.
LA  - eng
PT  - Journal Article
DEP - 20240114
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 82VFR53I78 (Aripiprazole)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Rats
MH  - Aripiprazole/pharmacology
MH  - *Schizophrenia/drug therapy
MH  - Dizocilpine Maleate/pharmacology
MH  - *Antipsychotic Agents/pharmacology
MH  - Electroencephalography
MH  - Receptors, N-Methyl-D-Aspartate
PMC - PMC10815955
OTO - NOTNLM
OT  - NMDAr hypofunction
OT  - aripiprazole
OT  - drug development
OT  - gamma-band ASSR
OT  - schizophrenia
OT  - spontaneous gamma oscillations
COIS- The authors declare no conflict of interest.
EDAT- 2024/01/23 06:42
MHDA- 2024/01/24 06:44
PMCR- 2024/01/14
CRDT- 2024/01/23 01:12
PHST- 2023/12/21 00:00 [received]
PHST- 2024/01/11 00:00 [revised]
PHST- 2024/01/12 00:00 [accepted]
PHST- 2024/01/24 06:44 [medline]
PHST- 2024/01/23 06:42 [pubmed]
PHST- 2024/01/23 01:12 [entrez]
PHST- 2024/01/14 00:00 [pmc-release]
AID - ijms25021035 [pii]
AID - ijms-25-01035 [pii]
AID - 10.3390/ijms25021035 [doi]
PST - epublish
SO  - Int J Mol Sci. 2024 Jan 14;25(2):1035. doi: 10.3390/ijms25021035.