Abstract | BACKGROUND: 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.
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Authors | Amir H Rezvani, Marty Cauley, Hannah Sexton, Yingxian Xiao, Milton L Brown, Mikell A Paige, Brian E McDowell, Kenneth J Kellar, Edward D Levin |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 215
Issue 4
Pg. 621-30
(Jun 2011)
ISSN: 1432-2072 [Electronic] Germany |
PMID | 21274704
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Azetidines
- Ligands
- Pyridines
- Receptors, Nicotinic
- nicotinic receptor alpha4beta2
- sazetidine-A
- Dizocilpine Maleate
- Scopolamine
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Topics |
- Animals
- Attention
(drug effects)
- Azetidines
(chemistry, pharmacology)
- Behavior, Animal
(drug effects)
- Cognition
(drug effects)
- Dizocilpine Maleate
(pharmacology)
- Dose-Response Relationship, Drug
- Drug Interactions
- Female
- Ligands
- Molecular Structure
- Photic Stimulation
- Psychomotor Performance
(drug effects)
- Pyridines
(chemistry, pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptors, Nicotinic
(metabolism)
- Scopolamine
(pharmacology)
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