title: Differences in prefrontal cortex GABA/glutamate ratio after acute restraint stress in rats are associated with specific behavioral and neurobiological patterns.
abstract: In patients suffering from stress-related pathologies and depression, frontal cortex GABA and glutamate contents are reported to decrease and increase, respectively. This suggests that the GABA and/or glutamate content may participate in pathological phenotype expression. Whether differences in frontal cortex GABA and glutamate contents would be associated with specific behavioral and neurobiological patterns remains unclear, especially in the event of exposure to moderate stress. We hypothesized that an increase in prefrontal cortex GABA/glutamate ratio would be associated with a blunted prefrontal cortex activation, an enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activation and changes in behavior. Rats being restrained for 1-h were then tested in an open-field test in order to assess their behavior while under stress, and were sacrificed immediately afterward. The GABA/glutamate ratio was assessed by (1)H high-resolution magic angle spinning magnetic resonance spectroscopy ((1)H-HRMAS-MRS). The neurobiological response was evaluated through prefrontal cortex mRNA expression and plasma corticosterone levels. The stressed rats were distributed into two subgroups according to their high (H-G/g) or low (L-G/g) GABA/glutamate ratio. Compared to the L-G/g rats, the H-G/g rats exhibited a decrease in c-fos, Arc, Npas4, Nr4a2 mRNA expression suggesting blunted prefrontal cortex activation. They also showed a more pronounced stress with an enhanced rise in corticosterone, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), creatine kinase (CK) and lactate dehydrogenase (LDH) levels, as well as behavioral disturbances with decreased locomotion speed. These changes were independent from prefrontal cortex energetic status as mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) pathway activities were similar in both subpopulations. The differences in GABA/glutamate ratio in the frontal cortex observed in the stressed animals may participate in shaping individual differences in psychophysiological reactions.
authors.affiliation: Département Neurosciences & Contraintes Opérationnelles, Institut de Recherche Biomédicale des Armées (IRBA), BP73, 91223 Brétigny-sur-Orge Cédex, France.
authors.forename: J-B
authors.initials: JB
authors.lastname: Drouet
authors.affiliation: Département Radiobiologie et de Radiopathologie, Institut de Recherche Biomédicale des Armées (IRBA), BP73, 91223 Brétigny-sur-Orge Cédex, France.
authors.forename: F
authors.initials: F
authors.lastname: Fauvelle
authors.affiliation: Département Radiobiologie et de Radiopathologie, Institut de Recherche Biomédicale des Armées (IRBA), BP73, 91223 Brétigny-sur-Orge Cédex, France.
authors.forename: S
authors.initials: S
authors.lastname: Maunoir-Regimbal
authors.affiliation: Département Neurosciences & Contraintes Opérationnelles, Institut de Recherche Biomédicale des Armées (IRBA), BP73, 91223 Brétigny-sur-Orge Cédex, France.
authors.forename: N
authors.initials: N
authors.lastname: Fidier
authors.affiliation: Département Neurosciences & Contraintes Opérationnelles, Institut de Recherche Biomédicale des Armées (IRBA), BP73, 91223 Brétigny-sur-Orge Cédex, France.
authors.forename: R
authors.initials: R
authors.lastname: Maury
authors.affiliation: Pôle de Génomique, Institut de Recherche Biomédicale des Armées (IRBA), BP73, 91223 Brétigny-sur-Orge Cédex, France.
authors.forename: A
authors.initials: A
authors.lastname: Peinnequin
authors.affiliation: Laboratoire d'analyses biologiques, Institut de Recherche Biomédicale des Armées (IRBA), BP73, 91223 Brétigny-sur-Orge Cédex, France.
authors.forename: J
authors.initials: J
authors.lastname: Denis
authors.affiliation: Quartier Campement, Ignié (PK-45), Congo.
authors.forename: A
authors.initials: A
authors.lastname: Buguet
authors.affiliation: Département Neurosciences & Contraintes Opérationnelles, Institut de Recherche Biomédicale des Armées (IRBA), BP73, 91223 Brétigny-sur-Orge Cédex, France; Ecole du Val de Grâce, 1 place Laveran, F-75005 Paris, France. Electronic address: frederic.canini@irba.fr.
authors.forename: F
authors.initials: F
authors.lastname: Canini
mesh_terms: D000208:Acute Disease; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000097:blood; D005106:Exploratory Behavior / Q000502:physiology*; D005971:Glutamates / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005971:Glutamates; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase; D003345:Corticosterone
keywords: GABA; glucocorticoids; glutamate; locomotion; prefrontal cortex