Increased exploratory activity and altered response to LSD in mice lacking the 5-HT(5A) receptor.
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.
Grailhe
R
R
Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA.
Waeber
C
C
Dulawa
S C
SC
Hornung
J P
JP
Zhuang
X
X
Brunner
D
D
Geyer
M A
MA
Hen
R
R
D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000503:physiopathology; D001345:Autoradiography; D005106:Exploratory Behavior / Q000502:physiology*; D006213:Hallucinogens / Q000494:pharmacology*; D007150:Immunohistochemistry; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000235:genetics / Q000502:physiology*; D013216:Reflex, Startle / Q000187:drug effects / Q000235:genetics / Q000502:physiology
D006213:Hallucinogens; D011985:Receptors, Serotonin; C078730:serotonin 5 receptor; D008238:Lysergic Acid Diethylamide