Attentional effects of nicotinic agonists in rats

• Published in: Neuropharmacology Vol. 44; no. 8; pp. 1054 - 1067
• Main Authors: Hahn, Britta, Sharples, Christopher G.V., Wonnacott, Susan, Shoaib, Mohammed, Stolerman, Ian P.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.06.2003; Elsevier
• Subjects: ABT-418; Animals; AR-R17779; Arecoline - analogs & derivatives; Arecoline - pharmacology; Attention; Attention - drug effects; Binding, Competitive; Biological and medical sciences; Brain - metabolism; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Bridged-Ring Compounds - pharmacology; Cell Line; Epibatidine; In Vitro Techniques; Isoarecolone; Isoxazoles - pharmacology; Male; Medical sciences; Nicotine; Nicotinic Agonists - pharmacology; Photic Stimulation; Pyridines - pharmacology; Pyrrolidines - pharmacology; Radioligand Assay; Rats; Spiro Compounds - pharmacology; ABT-418; Epibatidine; Isoarecolone; Attention; Nicotine; AR-R17779
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(03)00099-6

Nicotine can increase stimulus detection, response rate and speed in the five-choice serial reaction time task, a rodent test of attention. In the present experiments, four other nicotinic agonists with different pharmacological profiles were compared in the same procedure. The response profile of epibatidine resembled that previously obtained with nicotine in that response accuracy was enhanced and omission errors and correct response latency decreased. ABT-418 transiently increased accuracy in the first 10 min of test sessions and reduced response latency. Isoarecolone caused a dose-related increase in accuracy, but had no effect on omissions or response latency. This absence of effects on response rate- or speed-related measures may be related to its previously reported reduced ability to release dopamine as compared with nicotine. The α7-agonist AR-R17779 was without effect on any measure, indicating that this receptor subtype may not mediate nicotinic effects on attention. Affinity constants of compounds, determined in competition binding assays targeting the α4β2, α7, α3β4 and α3β2∗ nAChR subtypes, could not explain the differential behavioural effects observed. Differences in their functional efficacy at nAChR subtypes may instead be responsible. The finding that attentional performance and response rate and speed can be selectively modulated by nicotinic agonists is encouraging for the development of drugs with therapeutic properties similar to those of nicotine but with reduced unwanted effects.