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Extracellular glutamate release in the prefrontal cortex in rat models with relevance to schizophrenia

Roenker, Nicole
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1289237222

Abstract Details

2010, MS, University of Cincinnati, Pharmacy: Pharmaceutical Sciences.
Non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists produce psychotic symptoms in humans. In rodents, NMDA antagonists produce hyperlocomotion and stereotypies, as well as increased cortical glutamatergic neurotransmission. Several of the behaviors and cognitive impairment associated with NMDA receptor blockade appear to involve increased glutamatergic neurotransmission in the prefrontal cortex. In the present study, the increase in extracellular glutamate in the prefrontal cortex induced by MK-801 was examined in rats treated with antipsychotic agents, risperidone and paliperidone. In addition, the effects of the nitric oxide synthase inhibitor L-NAME and the GABAB receptor agonist baclofen were examined on the MK-801-induced glutamate increase in the prefrontal cortex. Furthermore basal and stimulated glutamate release in the prefrontal cortex was assessed in rats exposed prenatally to immune activation. Using in vivo microdialysis, it was determined that treatment with MK-801 (0.3 mg/kg, s.c.) significantly increased extracellular glutamate in the prefrontal cortex. The glutamate response to MK-801 was significantly attenuated in rats treated chronically for 21 days with risperidone (0.01 mg/kg/day) and paliperidone (0.01 mg/kg/day) in the drinking water, or in rats treated acutely with L-NAME (60 mg/kg, i.p.) or baclofen (5mg/kg, i.p.). Prenatal immune activation was achieved by treatment of pregnant rats on day 14 of gestation with polyinosinic:polycytidylic acid (poly I:C). Microdialysis was performed in male offspring on postnatal day 56, and it was determined the MK-801-induced increase in extracellular glutamate in the prefrontal cortex was significantly diminished in poly I:C-exposed rats. In addition, basal extracellular glutamate in the prefrontal cortex of poly I:C-exposed male rats were significantly greater than that in control animals. The elevated basal extracellular glutamate in the prefrontal cortex of poly I:C offspring was reduced to that of controls by paliperidone and to a lesser extent risperidone. These data support the view that increased extracellular glutamate in the prefrontal cortex in response to NMDA receptor blockade involves a nitergic and GABAergic mechanism and can be prevented by chronic antipsychotic drug treatment. It can be speculated further that the relative insensitivity of poly I:C exposed rats to NMDA receptor blockade may be indicative of a state of NMDA receptor hypofunction induced by prenatal immune activation.
Gary Gudelsky, PhD (Committee Chair)
Karen Gregerson, PhD (Committee Member)
Neil Richtand, MD (Committee Member)
60 p.
Pharmacology
schizophrenia; NMDA receptor; glutamate; prefrontal cortex

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Citations

  • Roenker, N. (2010). Extracellular glutamate release in the prefrontal cortex in rat models with relevance to schizophrenia [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1289237222

    APA Style (7th edition)

  • Roenker, Nicole. Extracellular glutamate release in the prefrontal cortex in rat models with relevance to schizophrenia. 2010. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1289237222.

    MLA Style (8th edition)

  • Roenker, Nicole. "Extracellular glutamate release in the prefrontal cortex in rat models with relevance to schizophrenia." Master's thesis, University of Cincinnati, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1289237222

    Chicago Manual of Style (17th edition)

ucin1289237222
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© 2010, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.