Increased exploratory activity and altered response to LSD in mice lacking the 5-HT(5A) receptor

Neuron. 1999 Mar;22(3):581-91. doi: 10.1016/s0896-6273(00)80712-6.

Abstract

In order to determine the distribution and function of the 5-HT5A serotonin receptor subtype, we generated knockout mice lacking the 5-HT5A gene. Comparative autoradiography studies of brains of wild-type (wt) and 5-HT5A knockout (5A-KO) mice revealed the existence of binding sites with high affinity for [125I]LSD that correspond to 5-HT5A receptors and that are concentrated in the olfactory bulb, neocortex, and medial habenula. When exposed to novel environments, the 5A-KO mice displayed increased exploratory activity but no change in anxiety-related behaviors. In addition, the stimulatory effect of LSD on exploratory activity was attenuated in 5A-KO mice. These results suggest that 5-HT5A receptors modulate the activity of neural circuits involved specifically in exploratory behavior and suggest that some of the psychotropic effects of LSD may be mediated by 5-HT5A receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Anxiety / physiopathology
  • Autoradiography
  • Exploratory Behavior / physiology*
  • Hallucinogens / pharmacology*
  • Immunohistochemistry
  • Lysergic Acid Diethylamide / pharmacology*
  • Male
  • Mice
  • Mice, Knockout
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / physiology*
  • Reflex, Startle / drug effects
  • Reflex, Startle / genetics
  • Reflex, Startle / physiology

Substances

  • Hallucinogens
  • Receptors, Serotonin
  • serotonin 5 receptor
  • Lysergic Acid Diethylamide