Reduction in Phencyclidine Induced Sensorimotor Gating Deficits in the Rat Following Increased System Xc − Activity in the Medial Prefrontal Cortex

Authors

Victoria Lutgen, Marquette University
Krista QualmannFollow
Jon M. Resch, Marquette UniversityFollow
Linghai KongFollow
Sujean Choi, Marquette UniversityFollow
David A. Baker, Marquette UniversityFollow

Document Type

Article

Language

eng

Format of Original

10 p.

Publication Date

4-2013

Publisher

Springer

Source Publication

Psychopharmacology

Source ISSN

0033-3158

Original Item ID

doi: 10.1007/s00213-012-2926-3

Abstract

Rationale: Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System x_c ⁻, a cystine–glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis.

Objectives: Our goal was to determine whether increased system x_c ⁻ activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating.

Methods: In situ hybridization was used to map messenger RNA (mRNA) expression of xCT, the active subunit of system x_c ⁻, in the prefrontal cortex. Prepulse inhibition was used to measure sensorimotor gating; deficits in prepulse inhibition were produced using phencyclidine (0.3–3 mg/kg, sc). N-Acetylcysteine (10–100 μM) and the system x_c ⁻ inhibitor (S)-4-carboxyphenylglycine (CPG, 0.5 μM) were used to increase and decrease system x_c ⁻ activity, respectively. The uptake of ¹⁴C-cystine into tissue punches obtained from the prefrontal cortex was used to assay system x_c ⁻ activity.

Results: The expression of xCT mRNA in the prefrontal cortex was most prominent in a lateral band spanning primarily the prelimbic cortex. Although phencyclidine did not alter the uptake of ¹⁴C-cystine in prefrontal cortical tissue punches, intraprefrontal cortical infusion of N-acetylcysteine (10–100 μM) significantly reduced phencyclidine- (1.5 mg/kg, sc) induced deficits in prepulse inhibition. N-Acetylcysteine was without effect when coinfused with CPG (0.5 μM), indicating an involvement of system x_c ⁻.

Conclusions: These results indicate that phencyclidine disrupts sensorimotor gating through system x_c ⁻ independent mechanisms, but that increasing cystine–glutamate exchange in the prefrontal cortex is sufficient to reduce behavioral deficits produced by phencyclidine.

Comments

Accepted version. Psychopharmacology, Vol. 226, No. 3 (April 2013): 531-540. DOI. © 2013 Springer. Used with permission.

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Recommended Citation

Lutgen, Victoria; Qualmann, Krista; Resch, Jon M.; Kong, Linghai; Choi, Sujean; and Baker, David A., "Reduction in Phencyclidine Induced Sensorimotor Gating Deficits in the Rat Following Increased System Xc − Activity in the Medial Prefrontal Cortex" (2013). Biomedical Sciences Faculty Research and Publications. 23.
https://epublications.marquette.edu/biomedsci_fac/23