Attentional effects of nicotinic agonists in rats.
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 alpha7-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 alpha4beta2, alpha7, alpha3beta4 and alpha3beta2* 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.
Hahn
Britta
B
Section of Behavioural Pharmacology, P049, Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK. bhahn@intra.nica.nih.gov
Sharples
Christopher G V
CG
Wonnacott
Susan
S
Shoaib
Mohammed
M
Stolerman
Ian P
IP
D000818:Animals; D001115:Arecoline / Q000031:analogs & derivatives* / Q000494:pharmacology; D001288:Attention / Q000187:drug effects*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002460:Cell Line; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010775:Photic Stimulation; D011725:Pyridines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D013141:Spiro Compounds / Q000494:pharmacology
C408128:AR-R 17779; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D007555:Isoxazoles; D018722:Nicotinic Agonists; D011725:Pyridines; D011759:Pyrrolidines; D013141:Spiro Compounds; C095493:isoarecolone; C088383:3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole; D001115:Arecoline; C082748:epibatidine