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Title: | Activation of thalamocortical networks by the N-methyl-D-aspartate receptor antagonist phencyclidine: reversal by clozapine |
Authors: | Santana, Noemí CSIC ORCID; Troyano-Rodriguez, Eva CSIC; Mengod Los Arcos, Guadalupe CSIC ORCID; Celada, Pau CSIC ORCID; Artigas, Francesc CSIC ORCID | Keywords: | Antipsychotics Delta oscillations GABAergic interneurons Glutamate Prefrontal cortex Pyramidal neurons Thalamus |
Issue Date: | 18-Jan-2011 | Publisher: | Elsevier | Citation: | Biological Psychiatry 69(10): 918-927 (2011) | Abstract: | [Background]: Noncompetitive N-methyl-D-aspartate receptor antagonists are widely used as pharmacological models of schizophrenia. Their neurobiological actions are still poorly understood, although the prefrontal cortex (PFC) appears as a key target area. [Methods]: We examined the effect of phencyclidine (PCP) on neuronal activity of the mediodorsal (MD) and centromedial (CM) thalamic nuclei, reciprocally connected with the PFC, using extracellular recordings (n = 50 neurons from 35 Wistar rats) and c-fos expression. [Results]: Phencyclidine (.25 mg/kg intravenous [IV]) markedly disorganized the activity of MD/CM neurons, increasing (424%) and decreasing (41%) the activity of 57% and 20% of the recorded neurons, respectively (23% remained unaffected). Phencyclidine reduced delta oscillations (.15–4 Hz) as assessed by recording local field potentials. The subsequent clozapine administration (1 mg/kg IV) reversed PCP effects on neuronal discharge and delta oscillations. Double in situ hybridization experiments revealed that PCP (10 mg/kg intraperitoneal [IP]) markedly increased c-fos expression in glutamatergic neurons of several cortical areas (prefrontal, somatosensory, retrosplenial, entorhinal) and in thalamic nuclei, including MD/CM. Phencyclidine also increased c-fos expression in the amygdala; yet, it had a small effect in the hippocampus. Phencyclidine did not increase c-fos expression in gamma-aminobutyric acidergic cells except in hippocampus, amygdala, somatosensory, and retrosplenial cortices. Clozapine (5 mg/kg IP) had no effect by itself but significantly prevented PCP-induced c-fos expression. [Conclusions]: Phencyclidine likely exerts its psychotomimetic action by increasing excitatory neurotransmission in thalamo-cortico-thalamic networks involving, among others, PFC, retrosplenial, and somatosensory cortices. The antipsychotic action of clozapine includes, among other actions, an attenuation of the neuronal hyperactivity in thalamocortical networks. |
Publisher version (URL): | http://dx.doi.org/doi:10.1016/j.biopsych.2010.10.030 | URI: | http://hdl.handle.net/10261/34529 | DOI: | 10.1016/j.biopsych.2010.10.030 | ISSN: | 0006-3223 | E-ISSN: | 1873-2402 |
Appears in Collections: | (IIBB) Artículos |
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