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In a Model of Neuroinflammation Designed to Mimic Delirium,Quetiapine Reduces Cortisol Secretion and Preserves Reversal Learning in the Attentional Set Shifting Task |
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| Authors: | Carr Zyad J. Miller Lauren Ruiz-Velasco Victor Kunselman Allen R. Karamchandani Kunal |
| Affiliation: | 1.Department of Anesthesiology & Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, 17033, USA ;2.Department of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, 17033, USA ;3.Department of Anesthesiology & Perioperative Medicine, H187, 500 University Dr., Hershey, PA, 17078, USA ;4.Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA ;5.Department of Public Health Sciences, Penn State College of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, 17033, USA ; |
| Abstract: | Quetiapine, an atypical antipsychotic medication has lacked pre-clinical validation for its purported benefits in the treatment of delirium. This laboratory investigation examined the effects of quetiapine on the attentional set shifting task (ASST), a measure of cognitive flexibility and executive functioning, in a rodent model of lipopolysaccharide (LPS) mediated neuroinflammation. 19 Sprague Dawley female rats were randomly selected to receive intraperitoneal placebo (N = 5), LPS and placebo (N = 7) or LPS and quetiapine (n = 7) and performed the ASST. We measured trials to criterion, errors, non-locomotion episodes and latency to criterion, serum cortisol and tumor necrosis factor alpha (TNF-α) levels. TNF-α levels were not different between groups at 24 h. Cortisol levels in the LPS + Quetiapine group were reduced compared to LPS + Placebo (P < 0.001) and did not differ from the placebo group (P = 0.15). Analysis between LPS + Quetiapine and LPS + Placebo treated rats demonstrated improvement in the compound discrimination reversal (CD Rev1) (P = 0.016) and the intra-dimensional reversal (ID Rev2) (P = 0.007) discriminations on trials to criterion. LPS + Quetiapine treated rats had fewer errors than LPS + Placebo treated animals in the compound discrimination (CD) (P = 0.007), CD Rev1 (P = 0.005), ID Rev2 (P < 0.001) discriminations. There was no difference in non-locomotion frequency or latency to criterion between the three groups in all discriminations (P > 0.0167). We demonstrated preserved reversal learning, no effect on attentional set shifting and normalized cortisol levels in quetiapine-treated rats in this neuroinflammatory model of delirium. This suggests that quetiapine’s beneficial effects in delirium may be related to the preservation of reversal learning and potential downstream effects related to reduction in cortisol production.  Graphical Abstract |
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