Is binding to nicotinic acetylcholine and dopamine receptors related to working memory in rats?
Nicotinic acetylcholine (ACh) and dopamine (DA) receptor activation has been found to be important for working memory. The regional distribution of these receptors in the brain has been well characterized. However, the relationship of the region-specific nicotinic ACh and DA binding density to memory performance has not been well assessed. In the current studies the relationship of receptor binding and memory function was examined. Receptor binding and memory performance were assessed in rats in three types of conditions: 1) chronic nicotine and mecamylamine vs. vehicle infusion; 2) lesions of the fimbria-fornix or medial basalocortical projection vs. sham lesions; and 3) 2-year-old aged rats vs. 3-month-old young adult rats. Nicotinic ACh receptors were labeled by [3H]N-methyl-carbamylcholine ([3H]MCC), D1 receptors by [3H]SCH 23390, and D2 receptors by [125I]iodosulpiride. Working memory was assessed using the radial-arm maze and T-maze delayed spatial alternation tasks. Chronic nicotine infusion substantially increased nicotinic receptor binding in a variety of brain areas and significantly improved working memory performance in the radial-arm maze. However, nicotinic 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, chronic effects of nicotine on nicotinic receptor binding and memory performance did not correlate in the aged rats. Nicotine also increased nicotinic receptor binding in the aged rats in brain areas except for the VTA, but did not improve memory performance. Lesions of the medial basalocortical projection or the fimbria-fornix did not cause significant changes in nicotinic binding in their target fields, but they did cause significant deficits in memory performance. Finally, there were no significant correlations of nicotinic binding in any brain region and memory performance. DA receptor binding was not altered by chronic nicotine or mecamylamine infusion, fimbria-fornix lesions, medial basalocortical lesions, or in aged rats. However, DA receptor binding did correlate with memory performance. There was a positive correlation of T-maze accuracy and D1 receptor binding in the frontal cortex and a negative correlation of T-maze accuracy and D1 receptor binding in the VTA and dentate gyrus. In contrast, a positive correlation was seen between radial-arm maze accuracy and D1 receptor binding in the VTA. Radial-arm maze accuracy was positively correlated with D2 receptor binding in the striatum and dentate gyrus. There are significant relationships between the extent of DA receptor binding and working memory, but relationship between nicotinic ACh receptor binding density and memory is weak.
Levin
E D
ED
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA.
Torry
D
D
Christopher
N C
NC
Yu
X
X
Einstein
G
G
Schwartz-Bloom
R D
RD
D000818:Animals; D004305:Dose-Response Relationship, Drug; D018782:Maze Learning / Q000187:drug effects*; D008464:Mecamylamine / Q000494:pharmacology*; D008568:Memory / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*
D011954:Receptors, Dopamine; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine