IS BINDING TO NICOTINIC ACETYLCHOLINE AND DOPAMINE-RECEPTORS RELATED TO WORKING-MEMORY IN RATS

Nicotinic acetylcholine (ACh) and dopamine (DA) receptor activation ha s been found to be important for working memory, The regional distribu tion of these receptors in the brain has been well characterized. Howe ver, the relationship of the region-specific nicotinic ACh and DA bind ing density to memory performance has not been well assessed, In the c urrent studies the relationship of receptor binding and memory functio n was examined, Receptor binding and memory performance were assessed in rats in three types of conditions: 1) chronic nicotine and mecamyla mine vs. vehicle infusion; 2) lesions of the fimbria-fornix or medial basalocortical projection vs, sham lesions; and 3) 2-year-old aged rat s vs. 3-month-old young adult rats, Nicotinic ACh receptors were label ed by [H-3]N-methyl-carbamylcholine ([H-3]MCC), D-1 receptors by [H-3] SCH 23390, and D-2 receptors by [I-125]iodosulpiride. Working memory w as assessed using the radial-arm maze and T-maze delayed spatial alter nation tasks. Chronic nicotine infusion substantially increased nicoti nic receptor binding in a variety of brain areas and significantly imp roved working memory performance in the radial-arm maze. However, nico tinic receptor binding did not correlate well with memory performance, The nicotinic antagonist mecamylamine did not block nicotine-induced increased nicotinic binding, but it did block nicotine-induced memory improvement. Aged rats relative to young adults showed both a decrease in nicotinic binding and impaired memory performance, However, chroni c effects of nicotine on nicotinic receptor binding and memory perform ance did not correlate in the aged rats, Nicotine also increased nicot inic receptor binding in the aged rats in brain areas except for the V TA, but did not improve memory performance, Lesions of the medial basa locortical projection or the fimbria-fornix did not cause significant changes in nicotinic binding in their target fields, but they did caus e significant deficits in memory performance, Finally, there were no s ignificant correlations of nicotinic binding in any brain region and m emory performance, DA receptor binding was not altered by chronic nico tine or mecamylamine infusion, fimbria-fornix lesions, medial basaloco rtical lesions, or in aged rats, However, DA receptor binding did corr elate with memory performance. There was a positive correlation of T-m aze accuracy and D-1 receptor binding in the frontal cortex and a nega tive correlation of T-maze accuracy and D-1 receptor binding in the VT A and dentate gyrus. In contrast, a positive correlation was seen betw een radial-arm maze accuracy and D-1 receptor binding in the VTA, Radi al-arm maze accuracy was positively correlated with D-2 receptor bindi ng in the striatum and dentate gyrus, There are significant relationsh ips between the extent of DA receptor binding and working memory, but relationship between nicotinic ACh receptor binding density and memory is weak. (C) 1997 Elsevier Science Inc.