Alpha7 nicotinic acetylcholine receptor activation ameliorates scopolamine-induced behavioural changes in a modified continuous Y-maze task in mice.
The alpha7 (alpha7) nicotinic acetylcholine receptor may represent a drug target for the treatment of disorders associated with working memory/attentional dysfunction. We investigated the effects of three distinct alpha7 nicotinic acetylcholine receptor agonists: 2-methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole (A-582941; 0.01-0.1 mg/kg), 4-bromophenyl 1,4-diazabicyclo(3.2.2) nonane-4-carboxylate (SSR180711; 0.3-3 mg/kg) and N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide (PNU-282987; 1-10 mg/kg), on scopolamine-induced deficits in a modified Y-maze procedure. Mice were forced to choose one of two visually distinct arms, and were confined there for a 5 min exploration period before being allowed to explore both arms for a 2 min test session, immediately thereafter. The time spent in each arm, entries and total distance travelled were recorded using an automated system. Characterisation experiments showed that scopolamine-treated (1 mg/kg) mice spent less time exploring the unfamiliar arm, when compared with vehicle-treated animals. Combination experiments showed that all three alpha7 agonists ameliorated scopolamine-induced changes in unfamiliar arm exploration. In conclusion, the present data support the idea that alpha7 nicotinic acetylcholine receptors may represent an interesting target for the treatment of conditions associated with attentional/working memory dysfunction.
Department of Affective Disorders, NeuroSearch A/S, Pederstrupvej 93, 2750 Ballerup, Denmark. JPR@neurosearch.dk
John P
JP
Redrobe
Elsebet Ø
EØ
Nielsen
Jeppe K
JK
Christensen
Dan
D
Peters
Daniel B
DB
Timmermann
Gunnar M
GM
Olsen
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018722:Nicotinic Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012601:Scopolamine / Q000494:pharmacology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579166:Chrna7 protein, mouse; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D012601:Scopolamine