Analysis of the role of 5-HT1A receptors in spatial and aversive learning in the rat.
The role of the brain 5-HT1A receptor in cognition was examined in the water maze (WM) and passive avoidance (PA) tasks in the male rat. Pre-training administration of the 5-HT1A receptor agonist 8-OH-DPAT impaired WM performance and facilitated PA retention at low doses (0.01 and 0.03 mg/kg) and impaired PA retention at higher doses (0.1-1.0 mg/kg). The 5-HT1A receptor antagonist NAD-299 produced a dose-dependent facilitation of PA retention. In contrast, the 5-HT1A receptor antagonists NAD-299 and WAY-100635 failed to alter acquisition and retention in the WM. The impairments in WM and PA (but not facilitation in PA) induced by 8-OH-DPAT were blocked by NAD-299. Furthermore, NAD-299 prevented the PA impairments induced by the muscarinic antagonist scopolamine or the NMDA receptor antagonist MK-801. In contrast, NAD-299 and WAY-100635 failed to attenuate the WM impairment induced by scopolamine, probably due to the failure of 5-HT1A receptor blockade to attenuate the sensorimotor disturbances induced by scopolamine. These results indicate that 5-HT1A receptor stimulation and blockade result in opposite effects in two types of cognitive tasks in the rat, and that 5-HT1A receptor blockade can facilitate some aspects of cognitive function, probably via modulation of cholinergic and glutamatergic transmissions. This suggests that 5-HT1A receptor antagonists may have a potential role in the treatment of human degenerative disorders associated with cognitive deficits.
Lüttgen
Maria
M
Division of Behavioral Neuroscience, Department of Neuroscience, B3:5, Retzius väg 8, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Elvander
Elin
E
Madjid
Nather
N
Ogren
Sven Ove
SO
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D001578:Benzopyrans; D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D016291:Dizocilpine Maleate; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012601:Scopolamine; C108607:robalzotan