Combined treatment with a 5HT1A receptor agonist and a muscarinic acetylcholine receptor antagonist disrupts water maze navigation behavior.
The present study was designed to investigate the effects of combined treatment with a serotonin (5-HT)1A receptor agonist, 8-hydroxy-2-(dipropylamino)-tetralin (8-OH-DPAT), and a muscarinic acetylcholine receptor antagonist, scopolamine, on water maze (WM) navigation. Treatment with either 8-OH-DPAT or scopolamine before daily behavioral training disrupted spatial navigation at medium doses and cue navigation at high doses. Pretraining treatment with a combination of subthreshold doses of 8-OH-DPAT and scopolamine impaired WM spatial and cue navigation, but did not impair the WM performance if the drugs were injected post-training. In trained rats, combined injections of subthreshold doses of 8-OH-DPAT and scopolamine given pretraining did not impair the rats' ability to find the platform in a familiar or in a novel position. The combination of 8-OH-DPAT and scopolamine also disrupted WM navigation in rats with central 5-HT depletion. A combination of a peripheral muscarinic acetylcholine receptor antagonist and 8-OH-DPAT had no effect on WM navigation. These data suggest that combined treatment with drugs blocking muscarinic acetylcholine receptors and activating 5-HT1A receptors greatly impairs WM learning/performance, but does not impair spatial memory per se.
Riekkinen
M
M
Department of Neurology, University of Kuopio, Finland.
Sirviö
J
J
Toivanen
T
T
Riekkinen
P
P
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D003463:Cues; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012601:Scopolamine / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013028:Space Perception / Q000187:drug effects*
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012601:Scopolamine; D010134:Fenclonine