Dorsal hippocampal alpha7 and alpha4beta2 nicotinic receptors and memory.
Nicotinic receptor systems have been shown to be important for working memory. In general, nicotinic agonists have been shown to improve memory, and nicotinic antagonists impair it. All of the neuronal substrates for nicotinic involvement in memory still remain to be discovered. The amygdala and ventral hippocampus have both been found to be important for nicotinic involvement in memory function. Local infusion of the nicotinic antagonist methyllycaconitine (MLA) to block alpha7 nicotinic receptors and dihydro-beta-erythrodine (DHbetaE) to block alpha4beta2 nicotinic receptors into the basolateral amygdala and the ventral hippocampus have been found to impair working memory function, with no additive effects being observed. The current project assessed the roles of alpha7 and alpha4beta2 nicotinic receptors in the dorsal hippocampus for memory function. Adult female Sprague-Dawley rats were trained on the 16-arm radial maze. The rats (n = 10) had bilateral cannulae implanted into the dorsal hippocampus. The rats were given acute infusions of DHbetaE (0, 1.69, 3.38, and 6.75 microg/side) and MLA (6.75 microg/side) alone and in combination in a repeated measures counter-balanced design. DHbetaE and MLA infusion into the dorsal hippocampus significantly increased working memory errors. However, when the two drugs were given in combination, an attenuated effect was seen. No significant effects of MLA or DHbetaE were seen with reference memory errors or response latency. These results confirm the importance of alpha4beta2 and alpha7 nicotinic acetylcholine receptors in the dorsal hippocampus for appetitively-motivated spatial cognitive function.
Nott
Alexi
A
Department of Psychiatry and Behavioral Sciences, Neurobehavioral Research Laboratory, Box #3412, Duke University Medical Center, Durham, NC 27710, USA.
Levin
Edward D
ED
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000502:physiology*; D013997:Time Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579165:Chrna7 protein, rat; D004338:Drug Combinations; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D000157:Aconitine