Subthalamic nucleus microinjections of 5-HT2 receptor antagonists suppress stereotypy in rats.
The subthalamic nucleus (STN) is an important mediator of basal ganglia output. We studied the effects of STN microinjections of the serotonin-2 (5-HT2) antagonists clozapine, mesulergine and M100,907 on apomorphine-induced stereotypic activity in the rat. Each compound profoundly decreased the expression of stereotypic behavior, with particularly strong effects to reduce gnawing behavior. Because M100,907 does not have appreciable affinity for dopamine D1 and D2 receptors, and since all three agents are 5-HT2 antagonists, the current data suggest that basal ganglia output related to orofacial movements can be significantly modified by 5-HT2 receptors. The results suggest that antipsychotics with serotonergic properties may have direct actions on the STN that influence their potential to produce orofacial and other motor side effects.
Barwick
V S
VS
Department of Psychiatry and Behavioral Science, Texas A&M University System Health Science Center, Temple 76504, USA.
Jones
D H
DH
Richter
J T
JT
Hicks
P B
PB
Young
K A
KA
D000818:Animals; D001058:Apomorphine; D001522:Behavior, Animal / Q000187:drug effects; D003024:Clozapine / Q000008:administration & dosage; D004873:Ergolines / Q000008:administration & dosage; D005464:Fluorobenzenes / Q000008:administration & dosage; D008297:Male; D008409:Mastication / Q000187:drug effects; D008845:Microinjections; D010880:Piperidines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000008:administration & dosage*; D019956:Stereotypic Movement Disorder / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000502:physiology*
D004873:Ergolines; D005464:Fluorobenzenes; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C079049:volinanserin; D003024:Clozapine; D001058:Apomorphine; C031649:mesulergine