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Effects of chronic sazetidine-A, a selective α4β2 neuronal nicotinic acetylcholine receptors desensitizing agent on pharmacologically-induced impaired attention in rats.

Publication ,  Journal Article
Rezvani, AH; Cauley, M; Xiao, Y; Kellar, KJ; Levin, ED
Published in: Psychopharmacology (Berl)
March 2013

RATIONALE: Nicotine and nicotinic agonists have been shown to improve attentional function. Nicotinic receptors are easily desensitized, and all nicotinic agonists are also desensitizing agents. Although both receptor activation and desensitization are components of the mechanism that mediates the overall effects of nicotinic agonists, it is not clear how each of the two opposed actions contributes to attentional improvements. Sazetidine-A has high binding affinity at α4β2 nicotinic receptors and causes a relatively brief activation followed by a long-lasting desensitization of the receptors. Acute administration of sazetidine-A has been shown to significantly improve attention by reversing impairments caused by the muscarinic cholinergic antagonist scopolamine and the NMDA glutamate antagonist dizocilpine. METHODS: In the current study, we tested the effects of chronic subcutaneous infusion of sazetidine-A (0, 2, or 6 mg/kg/day) on attention in Sprague-Dawley rats. Furthermore, we investigated the effects of chronic sazetidine-A treatment on attentional impairment induced by an acute administration of 0.02 mg/kg scopolamine. RESULTS: During the first week period, the 6-mg/kg/day sazetidine-A dose significantly reversed the attentional impairment induced by scopolamine. During weeks 3 and 4, the scopolamine-induced impairment was no longer seen, but sazetidine-A (6 mg/kg/day) significantly improved attentional performance on its own. Chronic sazetidine-A also reduced response latency and response omissions. CONCLUSIONS: This study demonstrated that similar to its acute effects, chronic infusions of sazetidine-A improve attentional performance. The results indicate that the desensitization of α4β2 nicotinic receptors with some activation of these receptors may play an important role in improving effects of sazetidine-A on attention.

Duke Scholars

Published In

Psychopharmacology (Berl)

DOI

EISSN

1432-2072

Publication Date

March 2013

Volume

226

Issue

1

Start / End Page

35 / 43

Location

Germany

Related Subject Headings

  • Scopolamine
  • Receptors, Nicotinic
  • Reaction Time
  • Rats, Sprague-Dawley
  • Rats
  • Pyridines
  • Psychiatry
  • Protein Binding
  • Muscarinic Antagonists
  • Ligands
 

Citation

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Rezvani, A. H., Cauley, M., Xiao, Y., Kellar, K. J., & Levin, E. D. (2013). Effects of chronic sazetidine-A, a selective α4β2 neuronal nicotinic acetylcholine receptors desensitizing agent on pharmacologically-induced impaired attention in rats. Psychopharmacology (Berl), 226(1), 35–43. https://doi.org/10.1007/s00213-012-2895-6
Rezvani, Amir H., Marty Cauley, Yingxian Xiao, Kenneth J. Kellar, and Edward D. Levin. “Effects of chronic sazetidine-A, a selective α4β2 neuronal nicotinic acetylcholine receptors desensitizing agent on pharmacologically-induced impaired attention in rats.Psychopharmacology (Berl) 226, no. 1 (March 2013): 35–43. https://doi.org/10.1007/s00213-012-2895-6.
Rezvani, Amir H., et al. “Effects of chronic sazetidine-A, a selective α4β2 neuronal nicotinic acetylcholine receptors desensitizing agent on pharmacologically-induced impaired attention in rats.Psychopharmacology (Berl), vol. 226, no. 1, Mar. 2013, pp. 35–43. Pubmed, doi:10.1007/s00213-012-2895-6.
Journal cover image

Published In

Psychopharmacology (Berl)

DOI

EISSN

1432-2072

Publication Date

March 2013

Volume

226

Issue

1

Start / End Page

35 / 43

Location

Germany

Related Subject Headings

  • Scopolamine
  • Receptors, Nicotinic
  • Reaction Time
  • Rats, Sprague-Dawley
  • Rats
  • Pyridines
  • Psychiatry
  • Protein Binding
  • Muscarinic Antagonists
  • Ligands