Skip to main content
Journal cover image

Sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor ligand: effects on dizocilpine and scopolamine-induced attentional impairments in female Sprague-Dawley rats.

Publication ,  Journal Article
Rezvani, AH; Cauley, M; Sexton, H; Xiao, Y; Brown, ML; Paige, MA; McDowell, BE; Kellar, KJ; Levin, ED
Published in: Psychopharmacology (Berl)
June 2011

BACKGROUND: Neuronal nicotinic receptor systems have been shown to play key roles in cognition. Nicotine and nicotinic analogs improve attention and nicotinic antagonists impair it. This study was conducted to investigate the role of α4β2 nicotinic receptors in sustained attention using a novel selective α4β2 nicotinic receptor ligand, sazetidine-A. METHODS: Female rats were trained to perform the signal detection task to a stable baseline of accuracy. The rats were injected with saline, sazetidine-A (0.01, 0.03, and 0.1 mg/kg), dizocilpine (0.05 mg/kg), or their combination; or, in another experiment, the rats were injected with the same doses of sazetidine-A, scopolamine (0.02 mg/kg), or their combination. RESULTS: Percent hit and percent correct rejection showed that dizocilpine caused significant (p < 0.025) impairments in performance, which were significantly reversed by each of the sazetidine-A doses. Response omissions were significantly (p < 0.05) increased by dizocilpine, and this was also significantly reversed by each of the sazetidine-A doses. None of the sazetidine-A doses had significant effects on hit, correct rejection, or response omissions when given alone. Scopolamine also caused significant (p < 0.0005) impairments in percent hit and percent correct rejection and increased response omissions, which were significantly attenuated by all the sazetidine-A doses for percent hit and response omissions and by the highest dose of sazetidine-A for percent correct rejection. Both scopolamine and dizocilpine significantly (p < 0.0005) increased response latency, an effect which was significantly attenuated by sazetidine-A coadministration. CONCLUSIONS: These studies imply an important role for α4β2 nicotinic receptors in improving sustained attention under conditions that disrupt it. Very low doses of sazetidine-A or drugs with a similar profile may provide therapeutic benefit for reversing attentional impairment in patients suffering from mental disorders and/or cognitive impairment.

Duke Scholars

Published In

Psychopharmacology (Berl)

DOI

EISSN

1432-2072

Publication Date

June 2011

Volume

215

Issue

4

Start / End Page

621 / 630

Location

Germany

Related Subject Headings

  • Scopolamine
  • Receptors, Nicotinic
  • Rats, Sprague-Dawley
  • Rats
  • Pyridines
  • Psychomotor Performance
  • Psychiatry
  • Photic Stimulation
  • Molecular Structure
  • Ligands
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rezvani, A. H., Cauley, M., Sexton, H., Xiao, Y., Brown, M. L., Paige, M. A., … Levin, E. D. (2011). Sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor ligand: effects on dizocilpine and scopolamine-induced attentional impairments in female Sprague-Dawley rats. Psychopharmacology (Berl), 215(4), 621–630. https://doi.org/10.1007/s00213-010-2161-8
Rezvani, Amir H., Marty Cauley, Hannah Sexton, Yingxian Xiao, Milton L. Brown, Mikell A. Paige, Brian E. McDowell, Kenneth J. Kellar, and Edward D. Levin. “Sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor ligand: effects on dizocilpine and scopolamine-induced attentional impairments in female Sprague-Dawley rats.Psychopharmacology (Berl) 215, no. 4 (June 2011): 621–30. https://doi.org/10.1007/s00213-010-2161-8.
Rezvani AH, Cauley M, Sexton H, Xiao Y, Brown ML, Paige MA, et al. Sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor ligand: effects on dizocilpine and scopolamine-induced attentional impairments in female Sprague-Dawley rats. Psychopharmacology (Berl). 2011 Jun;215(4):621–30.
Rezvani, Amir H., et al. “Sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor ligand: effects on dizocilpine and scopolamine-induced attentional impairments in female Sprague-Dawley rats.Psychopharmacology (Berl), vol. 215, no. 4, June 2011, pp. 621–30. Pubmed, doi:10.1007/s00213-010-2161-8.
Rezvani AH, Cauley M, Sexton H, Xiao Y, Brown ML, Paige MA, McDowell BE, Kellar KJ, Levin ED. Sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor ligand: effects on dizocilpine and scopolamine-induced attentional impairments in female Sprague-Dawley rats. Psychopharmacology (Berl). 2011 Jun;215(4):621–630.
Journal cover image

Published In

Psychopharmacology (Berl)

DOI

EISSN

1432-2072

Publication Date

June 2011

Volume

215

Issue

4

Start / End Page

621 / 630

Location

Germany

Related Subject Headings

  • Scopolamine
  • Receptors, Nicotinic
  • Rats, Sprague-Dawley
  • Rats
  • Pyridines
  • Psychomotor Performance
  • Psychiatry
  • Photic Stimulation
  • Molecular Structure
  • Ligands