Interaction between 5-HT1A and nicotinic cholinergic receptors in the regulation of water maze navigation behavior.

The interaction between serotonin (5-HT)1A and nicotinic cholinergic receptors in the regulation of spatial navigation behavior in the Morris water maze (WM) test was studied. Pretraining intraperitoneal (i.p.) injections of a combination of subthreshold doses of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (a 5-HT1A receptor agonist) at 30 micrograms/kg and mecamylamine (a nicotinic cholinergic receptor antagonist) a 2500 micrograms/kg greatly impaired WM navigation to a hidden platform and slightly, but not statistically significantly, impaired WM navigation to a visible platform. Post-training i.p. injections of this combination had no effect on WM navigation performance. Serotonin depletion induced by p-chlorophenylalanine (PCPA) increased the performance impairing action of pretraining injected combination of 8-OH-DPAT 30 micrograms/kg and mecamylamine 2500 micrograms/kg. In trained rats combined injections of 8-OH-DPAT 30 micrograms/kg and mecamylamine 2500 micrograms/kg given pretraining had no effect on the navigation to a hidden platform located in a familiar or in a novel position. Pretraining trial injected combination of hexamethonium 2000 micrograms/kg (a peripherally acting nicotinic antagonist) and 8-OH-DPAT 30 micrograms/kg had no effect on navigation. These data suggest that a combined treatment with a 5-HT1a receptor agonist and a nicotinic cholinergic receptor antagonist more severely impair non-mnemonic acquisition performance processes than consolidation and retrieval processes.