Acute phencyclidine administration induces c-Fos-immunoreactivity in interneurons in cortical and subcortical regions

Abstract

Dysfunction of N-Methyl-D-aspartate receptors (NMDARS) is believed to underlie some of the symptoms in schizophrenia, and non-competitive NMDAR antagonists (including phencyclidine (PCP)) are widely used as pharmacological schizophrenia models. Furthermore, mounting evidence suggests that impaired γ-aminobutyric acid (GABA) neurotransmission contributes to the cognitive deficits in schizophrenia. Thus alterations in GABAergic interneurons have been observed in schizophrenia patients and animal models. Acute systemic administration of PCP increases levels of c-Fos in several cortical and subcortical areas, but whether such induction occurs in specific populations of GABAergic interneuron subtypes still remains to be established. Overall, our data indicate that PCP activates a wide range of cortical and subcortical brain regions and that a substantial part of this activation is present in GABAergic interneurons in certain regions. This suggests that the psychotomimetic effect of PCP may be mediated via GABAergic interneurons.

Simultaneous effects on parvalbumin-positive interneuron and dopaminergic system development in a transgenic rat model for sporadic schizophrenia

“…Analysis was performed in the primary somatosensory cortex (S1), specifically in both the forelimb region (S1FL) and the barrel field (S1BF). Of note, changes in interneuron frequency in the somatosensory cortex have been reported in CMI patients 47 48 49 50 . Numbers of interneurons in both groups were compared in each cortical layer as well as the total cell count across all such layers.…”

P2X7 Receptor-Dependent Layer-Specific Changes in Neuron-Microglia Reactivity in the Prefrontal Cortex of a Phencyclidine Induced Mouse Model of Schizophrenia

“…Differences in PV interneuron activation were excluded from playing a role linked to the lower c-Fos immunoreactivity detected in PCP-treated P2rx7 −/− mice. It is worth mentioning that a previous c-Fos study reported an increase in PV interneuron activity in areas involved in acute PCP-induced hyperactivity, but different from the mPFC (Celada et al, 2013;Hervig et al, 2016). The detrimental effect of subchronic PCP models on prefrontal GABAergic interneurons is well documented (Piyabhan et al, 2019).…”

“…Systemic injection of PCP in rodents results in a psychotomimetic effect, characterized by hyper locomotor activity and stereotypical rotational behavior (Ishmael et al, 1998). Moreover, it is established that acute PCP administration alters the activity of several cortical and subcortical areas, which can be observed by the increased number of c-Fos expressing neurons (Celada et al, 2013;Hervig et al, 2016). In contrast, acute PCP administration in brain slices (Bourne et al, 1983;Wang and Liang, 1998) or local drug delivery in freely moving rats (Suzuki et al, 2002) inhibits most multi-synaptic excitatory neuronal activity.…”

Interneuron Heterotopia in the Lis1 Mutant Mouse Cortex Underlies a Structural and Functional Schizophrenia-Like Phenotype

“…Proteins coded by immediate-early genes such as cFOS , are considered markers of neuronal activity in the central nervous system ( Sagar et al, 1988 ; Herdegen et al, 1995 ; Kontkanen et al, 2002 ). Moreover, it has been established that the number of cFOS-expressing neurons increases in animal models of schizophrenia ( Celada et al, 2013 ; Hervig et al, 2016 ; Calovi et al, 2020 ). Here, we analyzed the distribution pattern of cFOS immunopositive cells in the hippocampal areas, mPFC, PERI, ECT, and ENT of both control and Lis1/sLis1 mutant mice.…”