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Phencyclidine Inhibits the Activity of Thalamic Reticular Gamma-Aminobutyric Acidergic Neurons in Rat Brain

  • Eva Troyano-Rodriguez
    Affiliations
    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
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  • Laia Lladó-Pelfort
    Affiliations
    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
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  • Noemi Santana
    Affiliations
    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
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  • Vicent Teruel-Martí
    Affiliations
    Deptartamento de Anatomia i Embriologia Humana, Facultat de Medicina, Universitat de València, Valencia, Spain
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  • Pau Celada
    Correspondence
    Address correspondence to Pau Celada, Ph.D., IIBB-CSIC (IDIBAPS), Department of Neurochemistry and Neuropharmacology, Rosselló 161, 6th Floor, 08036 Barcelona, Spain
    Affiliations
    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
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  • Francesc Artigas
    Affiliations
    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
    Search for articles by this author

      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.

      Key Words

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