title: Phencyclidine inhibits the activity of thalamic reticular gamma-aminobutyric acidergic neurons in rat brain.
abstract: BACKGROUND
  The neurobiological basis of action of noncompetitive N-methyl-D-aspartate acid receptor (NMDA-R) antagonists is poorly understood. Electrophysiological studies indicate that phencyclidine (PCP) markedly disrupts neuronal activity with an overall excitatory effect and reduces the power of low-frequency oscillations (LFO; <4 Hz) in thalamocortical networks. Because the reticular nucleus of the thalamus (RtN) provides tonic feed-forward inhibition to the rest of the thalamic nuclei, we examined the effect of PCP on RtN activity, under the working hypothesis that NMDA-R blockade in RtN would disinhibit thalamocortical networks.
  
  
  METHODS
  Drug effects (PCP followed by clozapine) on the activity of RtN (single unit and local field potential recordings) and prefrontal cortex (PFC; electrocorticogram) in anesthetized rats were assessed.
  
  
  RESULTS
  PCP (.25-.5 mg/kg, intravenous) reduced the discharge rate of 19 of 21 RtN neurons to 37% of baseline (p < .000001) and the power of LFO in RtN and PFC to ~20% of baseline (p < .001). PCP also reduced the coherence between PFC and RtN in the LFO range. A low clozapine dose (1 mg/kg intravenous) significantly countered the effect of PCP on LFO in PFC but not in RtN and further reduced the discharge rate of RtN neurons. However, clozapine administration partly antagonized the fall in coherence and phase-locking values produced by PCP.
  
  
  CONCLUSIONS
  PCP activates thalamocortical circuits in a bottom-up manner by reducing the activity of RtN neurons, which tonically inhibit thalamic relay neurons. However, clozapine reversal of PCP effects is not driven by restoring RtN activity and may involve a cortical action.
authors.affiliation: Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomèdiques de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental, Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Troyano-Rodriguez
authors.affiliation: Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomèdiques de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental, Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Lladó-Pelfort
authors.affiliation: Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomèdiques de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental, Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Noemi
authors.initials: N
authors.lastname: Santana
authors.affiliation: Deptartamento de Anatomia i Embriologia Humana, Facultat de Medicina, Universitat de València, Valencia, Spain.
authors.forename: Vicent
authors.initials: V
authors.lastname: Teruel-Martí
authors.affiliation: Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomèdiques de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental, Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. Electronic address: pau.celada@iibb.csic.es.
authors.forename: Pau
authors.initials: P
authors.lastname: Celada
authors.affiliation: Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomèdiques de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental, Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Artigas
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D003024:Clozapine / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects*; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D010320:Parvalbumins / Q000378:metabolism; D010622:Phencyclidine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000166:cytology*
chemical_list: D018756:GABA Antagonists; D006213:Hallucinogens; D010320:Parvalbumins; D010622:Phencyclidine; D003024:Clozapine
keywords: Antipsychotic drugs; NMDA receptor antagonists; clozapine; psychotic symptoms; schizophrenia; thalamocortical networks