title: The dopamine D1 receptor agonist SKF 38393 improves temporal order memory performance in maternally deprived rats.
abstract: Previously, we showed that maternal deprivation (MD) (3h/day, postnatal-day 1-14) impaired the performance at adulthood in the object temporal order memory task (TMT) that principally implicates the medial prefrontal cortex (mPFC). Dopamine (DA) transmission in the PFC may play a critical role in the achievement of the TMT. Here, to investigate whether MD could results in dysfunction of the DA system in the mPFC, we assessed in this region the tissue contents and extracellular levels of DA and its metabolites, as the density of D1 receptor. Besides we examined whether an agonist of the DA receptor D1, the SKF38393, could have a beneficial effect on the performance of deprived (D) rats in the TMT. We observed that MD induced a significant reduction of the extracellular level of DOPAC in the mPFC and in the density of the D1 receptor in the anterior cingulate cortex, a sub-region of mPFC. On the other hand, we observed that an acute systemic injection of a D1 receptor agonist, SKF38393, was effective to correct the memory deficiency of D rats in the TMT, when administered before the retrieval phase. We showed that a stress suffered by rats during the perinatal period led to dysfunction of the adult DA system, possibly triggering greater vulnerability to cognitive and mood disorders. Interestingly, an acute administration of a D1 receptor agonist in adulthood was sufficient to improve the deficit in the temporal memory. A better understanding of this phenomenon would permit the development of treatments adapted to patients with a history of early traumatic experiences.
authors.affiliation: INSERM, UMRs 952, Physiopathologie des Maladies du Système Nerveux Central, 9 quai Saint Bernard, F-75005 Paris, France; CNRS, UMR 7224, Physiopathologie des Maladies du Système Nerveux Central, 9 quai Saint Bernard, F-75005 Paris, France; UPMC Univ. Paris 06, Physiopathologie des Maladies du Système Nerveux Central, F-75005 Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lejeune
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dourmap
authors.forename: Marie-Pascale
authors.initials: MP
authors.lastname: Martres
authors.forename: Bruno
authors.initials: B
authors.lastname: Giros
authors.forename: Valérie
authors.initials: V
authors.lastname: Daugé
authors.forename: Laurent
authors.initials: L
authors.lastname: Naudon
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D008297:Male; D008426:Maternal Deprivation; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D015102:3,4-Dihydroxyphenylacetic Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004298:Dopamine
keywords: D1 receptor autoradiography; HPLC; Maternal deprivation; Microdialysis; Prefrontal cortex; Temporal order memory task