Corticotropin releasing factor in the nucleus basalis of Meynert impairs attentional performance and reduces levels of glutamate and taurine in male and female rats. (15th December 2022)

• Record Type: Journal Article
• Authors: Eck, Samantha R.; Kokras, Nikolaos; Wicks, Brittany; Baltimas, Petros; Hall, Arron; van Bendegem, Nina; Salvatore, Madeleine; Cohen, Sarah R.; Bergmann, Joy; Ceretti, Attilio; Parikh, Vinay; Dalla, Christina; Bangasser, Debra A.
• Is Part Of: Neuropharmacology. Volume 221(2022)
• Publication Date: 2022-12-15
• Subjects: Attention -- Basal forebrain -- Cognition -- Glutamate -- Stress; aCSF artificial cerebrospinal fluid -- ADHD attention deficit hyperactivity disorder -- CRF corticotropin releasing factor -- HPLC high performance liquid chromatography -- NBM nucleus basalis of Meynert -- mPFC medial prefrontal cortex -- PTSD post-traumatic stress disorder -- SAT sustained attention task; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2022.109280
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Psychiatric disorders that are characterized by impairments in sustained attention, including attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), and major depression are also sensitive to exacerbation by stress. Sustained attention relies on cholinergic and non-cholinergic projections from the nucleus basalis of Meynert (NBM) in the basal forebrain to the medial prefrontal cortex (mPFC). We have previously shown that central administration of the stress neuropeptide corticotropin releasing factor (CRF) impairs performance on the sustained attention task (SAT) in adult male and female rats. The present study investigated whether this effect was mediated by CRF's action in the NBM. Rats were administered CRF in the NBM and subsequent SAT performance was measured. A high dose of CRF (100 ng) significantly impaired performance on non-signaled events across sex. Because performance on non-signaled events is believed to depend on non-cholinergic (i.e., GABA and glutamate) signaling, high performance liquid chromatography was used to quantify amino acid levels in the NBM and mPFC. We found females have higher levels of glutamate, glutamine, GABA glycine, and alanine in the NBM than males. Importantly, CRF in the NBM led to a local decrease of taurine and several amino acids involved in glutamate synthesis in males and females, changes which may mediate the CRF-induced SAT performance deficit. Together these studies suggest that CRF regulation of amino acids in the NMB contributes to stress-induced attention deficits. Highlights: CRF in the NBM impaired sustained attention. CRF in the NBM decreased NBM levels of amino acids involved in glutamate synthesis. CRF in the NBM decreased NBM taurine levels. There are baseline sex differences in mPFC and NBM amino acid levels. These data suggest CRF disrupts attention by suppressing glutamate and taurine.