Analysis of the role of 5-HT1A receptors in spatial and aversive learning in the rat

Neuropharmacology. 2005 May;48(6):830-52. doi: 10.1016/j.neuropharm.2005.01.007.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Analysis of Variance
  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology*
  • Behavior, Animal / drug effects
  • Benzopyrans / pharmacology
  • Dizocilpine Maleate / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Excitatory Amino Acid Antagonists / pharmacology
  • Male
  • Maze Learning / drug effects
  • Muscarinic Antagonists / pharmacology
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Receptor, Serotonin, 5-HT1A / physiology*
  • Scopolamine / pharmacology
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Spatial Behavior / drug effects
  • Spatial Behavior / physiology*
  • Time Factors


  • Benzopyrans
  • Excitatory Amino Acid Antagonists
  • Muscarinic Antagonists
  • Piperazines
  • Pyridines
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • Dizocilpine Maleate
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Scopolamine
  • robalzotan