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Chronic nicotine and dizocilpine effects on nicotinic and NMDA glutamatergic receptor regulation: interactions with clozapine actions and attentional performance in rats.

Publication ,  Journal Article
Rezvani, AH; Tizabi, Y; Getachew, B; Hauser, SR; Caldwell, DP; Hunter, C; Levin, ED
Published in: Prog Neuropsychopharmacol Biol Psychiatry
May 15, 2008

Blockade of NMDA glutamate receptors with dizocilpine (MK-801) has been shown to cause substantial cognitive deficits and has been used to model symptoms of schizophrenia. Nicotine or nicotinic agonists, in contrast, may enhance cognitive or attentional functions and be of therapeutic potential in schizophrenia. Nicotinic-glutamatergic interactions, therefore, may have important implications in cognitive functions and antipsychotic treatments. Clozapine, a widely used antipsychotic drug, has been shown in some studies to be effective in ameliorating the cognitive deficits associated with schizophrenia. However, there is some evidence to suggest that clozapine similar to haloperidol may impair sustained attention in rats. In this study, we sought to determine whether chronic nicotine or dizocilpine may modify the effects of acute clozapine on attentional parameters and whether the behavioral effects would correlate with nicotinic or NMDA receptor densities in discrete brain regions. Adult female rats trained on an operant visual signal detection task were given 4 weeks of nicotine (5 mg/kg/day), dizocilpine (0.15 mg/kg/day), the same doses of both nicotine and dizocilpine as a mixture, or saline by osmotic minipump. While on chronic treatment, rats received acute injections of various doses of clozapine (0, 0.625, 1.25, 2.5 mg/kg, sc) 10 min prior to tests on attentional tasks. The pumps were removed on day 28 and 24 h later the animals were sacrificed for measurements of receptor densities in specific brain regions. The percent correct hit as a measure of sustained attention was significantly impaired by clozapine in a dose-related manner. Neither chronic nicotine nor dizocilpine affected this measure on their own or modified the effects of clozapine. Both nicotine and dizocilpine affected the receptor bindings in a region specific manner and their combination further modified the effects of each other in selective regions. Attentional performance was inversely correlated with alpha-bungarotoxin binding in the frontal cortex only. In conclusion, the data suggest attentional impairments with clozapine alone and no modification of this effect with nicotine or dizocilpine. Moreover, cortical low affinity nicotinic receptors may have a role in attentional functions.

Duke Scholars

Published In

Prog Neuropsychopharmacol Biol Psychiatry

DOI

ISSN

0278-5846

Publication Date

May 15, 2008

Volume

32

Issue

4

Start / End Page

1030 / 1040

Location

England

Related Subject Headings

  • Signal Detection, Psychological
  • Receptors, Nicotinic
  • Receptors, N-Methyl-D-Aspartate
  • Rats, Sprague-Dawley
  • Rats
  • Quinolizines
  • Psychomotor Performance
  • Psychiatry
  • Nicotinic Agonists
  • Nicotine
 

Citation

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ICMJE
MLA
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Rezvani, A. H., Tizabi, Y., Getachew, B., Hauser, S. R., Caldwell, D. P., Hunter, C., & Levin, E. D. (2008). Chronic nicotine and dizocilpine effects on nicotinic and NMDA glutamatergic receptor regulation: interactions with clozapine actions and attentional performance in rats. Prog Neuropsychopharmacol Biol Psychiatry, 32(4), 1030–1040. https://doi.org/10.1016/j.pnpbp.2008.01.018
Rezvani, Amir H., Yousef Tizabi, Bruk Getachew, Sheketha R. Hauser, D Patrick Caldwell, Christopher Hunter, and Edward D. Levin. “Chronic nicotine and dizocilpine effects on nicotinic and NMDA glutamatergic receptor regulation: interactions with clozapine actions and attentional performance in rats.Prog Neuropsychopharmacol Biol Psychiatry 32, no. 4 (May 15, 2008): 1030–40. https://doi.org/10.1016/j.pnpbp.2008.01.018.
Rezvani AH, Tizabi Y, Getachew B, Hauser SR, Caldwell DP, Hunter C, et al. Chronic nicotine and dizocilpine effects on nicotinic and NMDA glutamatergic receptor regulation: interactions with clozapine actions and attentional performance in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2008 May 15;32(4):1030–40.
Rezvani, Amir H., et al. “Chronic nicotine and dizocilpine effects on nicotinic and NMDA glutamatergic receptor regulation: interactions with clozapine actions and attentional performance in rats.Prog Neuropsychopharmacol Biol Psychiatry, vol. 32, no. 4, May 2008, pp. 1030–40. Pubmed, doi:10.1016/j.pnpbp.2008.01.018.
Rezvani AH, Tizabi Y, Getachew B, Hauser SR, Caldwell DP, Hunter C, Levin ED. Chronic nicotine and dizocilpine effects on nicotinic and NMDA glutamatergic receptor regulation: interactions with clozapine actions and attentional performance in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2008 May 15;32(4):1030–1040.
Journal cover image

Published In

Prog Neuropsychopharmacol Biol Psychiatry

DOI

ISSN

0278-5846

Publication Date

May 15, 2008

Volume

32

Issue

4

Start / End Page

1030 / 1040

Location

England

Related Subject Headings

  • Signal Detection, Psychological
  • Receptors, Nicotinic
  • Receptors, N-Methyl-D-Aspartate
  • Rats, Sprague-Dawley
  • Rats
  • Quinolizines
  • Psychomotor Performance
  • Psychiatry
  • Nicotinic Agonists
  • Nicotine