title: Modulation of the subthalamic nucleus activity by serotonergic agents and fluoxetine administration.
abstract: BACKGROUND
  Within the basal ganglia, the subthalamic nucleus (STN) is the only glutamatergic structure and occupies a central position in the indirect pathway. In rat, the STN receives serotonergic input from the dorsal raphe nucleus and expresses serotonergic receptors.
  
  
  OBJECTIVE
  This study examined the consequences of serotonergic neurotransmission modulation on STN neuron activity.
  
  
  METHODS
  In vivo single-unit extracellular recordings, HPLC determination, and rotarod and bar test were performed in control, 4-chloro-DL-phenylalanine methyl ester hydrochloride- (pCPA, a serotonin synthesis inhibitor) and chronically fluoxetine-treated rats.
  
  
  RESULTS
  The pCPA treatment and the administration of serotonin (5-HT) receptor antagonists increased number of bursting neurons in the STN. The systemic administration of the 5-HT(1A) agonist, 8-OH-DPAT, decreased the firing rate and increased the coefficient of variation of STN neurons in pCPA-treated rats but not in control animals. Additionally, microinjection of 8-OH-DPAT into the STN reduced the firing rate of STN neurons, while microinjection of the 5-HT(2C) agonist, Ro 60-0175, increased the firing rate in both control and fluoxetine-treated animals. Finally, the fluoxetine challenge increased the firing rate of STN neurons in fluoxetine-treated rats and induced catalepsy.
  
  
  CONCLUSIONS
  Our results indicate that the depletion and the blockage of 5-HT modify STN neuron firing pattern. STN neuron activity is under the control of 5-HT(1A) and 5-HT(2C) receptors located both inside and outside the STN. Finally, fluoxetine increases STN neuron activity in chronically fluoxetine-treated rats, which may explain the role of this nucleus in fluoxetine-induced extrapyramidal side effects.
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, 48940, Leioa, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Aristieta
authors.forename: T
authors.initials: T
authors.lastname: Morera-Herreras
authors.forename: J A
authors.initials: JA
authors.lastname: Ruiz-Ortega
authors.forename: C
authors.initials: C
authors.lastname: Miguelez
authors.forename: I
authors.initials: I
authors.lastname: Vidaurrazaga
authors.forename: A
authors.initials: A
authors.lastname: Arrue
authors.forename: M
authors.initials: M
authors.lastname: Zumarraga
authors.forename: L
authors.initials: L
authors.lastname: Ugedo
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D005021:Ethylamines / Q000494:pharmacology; D010134:Fenclonine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020531:Subthalamic Nucleus / Q000187:drug effects* / Q000502:physiology
chemical_list: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D005021:Ethylamines; D010134:Fenclonine; D005473:Fluoxetine; D007211:Indoles; D044282:Receptor, Serotonin, 5-HT1A; D044405:Receptor, Serotonin, 5-HT2C; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C103848:Ro 60-0175; C020261:4-chlorophenylalanine methyl ester