Acute administration of phencyclidine induces tonic activation of medial prefrontal cortex neurons in freely moving rats

Suzuki, Yoshiaki; Jodo, Eiichi; Takeuchi, Satoshi; Niwa, Shin Ichi; Kayama, Yukihiko

doi:10.1016/s0306-4522(02)00298-1

Cited by 102 publications

(85 citation statements)

References 44 publications

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“…The fact that local perfusion of PCP, ketamine, and MK-801 in the mPFC failed to elicit the increase in glutamate and/or 5-HT (Lorrain et al, 2003;Amargós-Bosch et al, 2006, this study) indicates that the NMDA receptors responsible for these effects are located outside the mPFC. Our results are consistent with other data showing that the increased locomotion and firing or EPSCs of putative pyramidal neurons of the mPFC following systemic administration of NMDA receptor antagonists (Suzuki et al, 2002;Jodo et al, 2003;Jackson et al, 2004) were not mimicked by intra-mPFC application of these compounds (Aghajanian and Marek, 2000;Suzuki et al, 2002;Jodo et al, 2005). What is the actual localization of these NMDA receptors and the source of the cortical hyperglutamatergic transmission induced by their blockade?…”

Section: Discussionsupporting

confidence: 92%

“…Acute NMDA receptor antagonism has also been reported to increase the release of glutamate (Moghaddam et al, 1997;Adams and Moghadam, 2001;Lorrain et al, 2003), dopamine (Moghaddam and Adams, 1998;Mathé et al, 1999;Schmidt and Fadayel, 1996), and serotonin (5-HT) (Martin et al, 1998;Millan et al, 1999;Adams and Moghadam, 2001;Amargós-Bosch et al, 2006) in the medial prefrontal cortex (mPFC) of rats. These effects are coincident with an enhanced spontaneous firing rate of putative pyramidal neurons of the mPFC (Suzuki et al, 2002;Jackson et al, 2004). The increase in cortical glutamatergic transmission elicited through the blockade of an excitatory glutamate receptor (NMDA) may seem contradictory.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, theoretically, this glutamatergic disinhibition could occur in the mPFC and/or in areas sending glutamatergic projections to the mPFC. However, the intra-mPFC administration of PCP or ketamine was unable to elevate cell firing and locomotion (Suzuki et al, 2002) or increase extracellular 5-HT (Amargós-Bosch et al, 2006). Therefore, it appears that the NMDA receptors responsible for these effects are located outside the mPFC, possibly in GABA neurons that would tonically inhibit glutamatergic efferents in areas that project densely to mPFC, such as hippocampus, thalamus, or amygdala.…”

Section: Introductionmentioning

confidence: 99%

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Clozapine and Haloperidol Differently Suppress the MK-801-Increased Glutamatergic and Serotonergic Transmission in the Medial Prefrontal Cortex of the Rat

López-Gil

Babot

Amargós-Bosch

et al. 2007

Neuropsychopharmacol

166

158

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The administration of noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine and ketamine has been shown to increase the extracellular concentration of glutamate and serotonin (5-HT) in the medial prefrontal cortex (mPFC). In the present work, we used in vivo microdialysis to examine the effects of the more potent noncompetitive NMDA receptor antagonist, MK-801, on the efflux of glutamate and 5-HT in the mPFC, and whether the MK-801-induced changes in the cortical efflux of both transmitters could be blocked by clozapine and haloperidol given systemically or intra-mPFC. The systemic, but not the local administration of MK-801, induced an increased efflux of 5-HT and glutamate, which suggests that the NMDA receptors responsible for these effects are located outside the mPFC, possibly in GABAergic neurons that tonically inhibit glutamatergic inputs to the mPFC. The MK-801-induced increases of extracellular glutamate and 5-HT were dependent on nerve impulse and the activation of mPFC AMPA/ kainate receptors as they were blocked by tetrodotoxin and NBQX, respectively. Clozapine and haloperidol blocked the MK-801-induced increase in glutamate, whereas only clozapine was able to block the increased efflux of 5-HT. The local effects of clozapine and haloperidol paralleled those observed after systemic administration, which emphasizes the relevance of the mPFC as a site of action of these antipsychotic drugs in offsetting the neurochemical effects of MK-801. The ability of clozapine to block excessive cortical 5-HT efflux elicited by MK-801 might be related to the superior efficacy of this drug in treating negative/cognitive symptoms of schizophrenia.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clozapine and Haloperidol Differently Suppress the MK-801-Increased Glutamatergic and Serotonergic Transmission in the Medial Prefrontal Cortex of the Rat

López-Gil

Babot

Amargós-Bosch

et al. 2007

Neuropsychopharmacol

166

158

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“…PCP induces schizophrenia-like symptoms in humans and frontal cortical dysfunction with corresponding symptoms of schizophrenia in non-human animals (Cohen et al, 1962;Moghaddam and Adams, 1998;Stefani and Moghaddam, 2002;Domino and Luby, 2012). In rodents, previous in vivo studies have shown that systemic administration of PCP elicits long-lasting activation of mPFC neurons, which occurs primarily via excitatory afferent inputs (Jodo et al, 2003;Suzuki et al, 2002). Injection of the NMDA channel blocker PCP attenuated the BLA-mediated inhibition of hippocampal-evoked firing, abolishing the timing-dependent inhibition that was observed under control conditions.…”

Section: Modulatory Influence Of Bla On Vhipp-evoked Firing In Mpfc Imentioning

confidence: 99%

Afferent Drive of Medial Prefrontal Cortex by Hippocampus and Amygdala is Altered in MAM-Treated Rats: Evidence for Interneuron Dysfunction

Esmaeili

Grace

2013

Neuropsychopharmacol

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Evidence indicates that the prefrontal cortex and its regulation by afferent inputs are disrupted in schizophrenia. Using a validated rat model of schizophrenia based on prenatal administration of the mitotoxin methyl azoxymethanol acetate (MAM), we examined the convergent projections from the ventral hippocampus (vHipp) and the basolateral amygdala (BLA) in the medial prefrontal cortex (mPFC). In vivo extracellular recordings were done in anesthetized rats to assess how prior stimulation of the BLA or vHipp input to the mPFC affected mPFC responses to subsequent stimulation of these regions. The interstimulus interval (ISI) of the BLA and vHipp pulse stimulation was varied randomly between 0 and 130 ms, and the probability of evoked spike response in the mPFC measured. We found that BLA input increased vHipp-evoked spike probability at ISIs 40-130 ms, but decreased spike probability at ISIs 10-20 ms. This would be consistent with activation of inhibitory interneurons at shorter ISIs by BLA stimulation. In contrast, in MAM-treated rats BLA stimulation increased vHipp-evoked spike probability in mPFC at all ISIs tested. Given that interneurons are driven primarily by N-methyl-D-aspartate (NMDA) channel activation, the effects of the NMDA channel blocker, phencyclidine (PCP), were tested. PCP was found to completely attenuate the inhibitory effect of BLA input on vHipp-evoked responses in mPFC at shorter ISIs, causing the response in control rats treated with PCP to resemble that observed in the MAM rat. In contrast to the effects of BLA stimulation on vHipp-mPFCevoked responses, there was no inhibitory period when examining the effects of vHipp stimulation on BLA-mPFC-evoked responses in control rats, but in MAM-treated rats there was a significant inhibition at short intervals. Thus, both affective input arising from the BLA and context-dependent input from the vHipp exert a modulatory effect on mPFC neural activity in response to these inputs. Whereas the BLA potentiated vHipp input to the mPFC at long intervals, there was a short-interval inhibitory period that appeared to be mediated by an NMDA-dependent drive of interneurons. This inhibitory modulation was absent in the model of schizophrenia and following PCP, which is consistent with an interneuron disruption in this disorder.

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“…The PFC is an important site for psychosis and cognitive problems related to schizophrenia, and it has been shown that acute systemic administration of ketamine or PCP rapidly increases PFC metabolic activity in parallel with PFC-related psychotic symptoms in healthy individuals (Vollenweider et al 1997;Breier et al 1997;Lewis, 2012). Likewise, studies in rats have shown rapid increases in PFC neuronal firing and expression of immediate-early genes following acute NMDAR antagonism (including PCP) (Suzuki et al 2002;Gao et al 1993Gao et al , 1998. This increase in PFC activity has been observed to be followed by a delayed depression of activity over a 24 hours period followed (Gao et al 1993(Gao et al , 1998, which may be relevant to the decrease in PFC activity 5 seen in schizophrenia patients.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.

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Acute administration of phencyclidine induces tonic activation of medial prefrontal cortex neurons in freely moving rats

Cited by 102 publications

References 44 publications

Clozapine and Haloperidol Differently Suppress the MK-801-Increased Glutamatergic and Serotonergic Transmission in the Medial Prefrontal Cortex of the Rat

Clozapine and Haloperidol Differently Suppress the MK-801-Increased Glutamatergic and Serotonergic Transmission in the Medial Prefrontal Cortex of the Rat

Afferent Drive of Medial Prefrontal Cortex by Hippocampus and Amygdala is Altered in MAM-Treated Rats: Evidence for Interneuron Dysfunction

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

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