Evidence for involvement of nitric oxide and GABAB receptors in MK-801- stimulated release of glutamate in rat prefrontal cortex

We have tested the hypothesis that cerebral nitric oxide (NO) production is involved in hyperbaric O2 (HBO2) neurotoxicity. Regional cerebral blood flow (rCBF) and electroencephalogram (EEG) were measured in anesthetized rats during O2 exposure to 1, 3, 4, and 5 ATA with or without administration of the NO synthase inhibitor ( N ω-nitro-l-arginine methyl ester), l-arginine, NO donors, or the N-methyl-d-aspartate receptor inhibitor MK-801. After 30 min of O2 exposure at 3 and 4 ATA, rCBF decreased by 26–39% and by 37–43%, respectively, and was sustained for 75 min. At 5 ATA, rCBF decreased over 30 min in the substantia nigra by one-third but, thereafter, gradually returned to preexposure levels, preceding the onset of EEG spiking activity. Rats pretreated with N ω-nitro-l-arginine methyl ester and exposed to HBO2 at 5 ATA maintained a low rCBF. MK-801 did not alter the cerebrovascular responses to HBO2at 5 ATA but prevented the EEG spikes. NO donors increased rCBF in control rats but were ineffective during HBO2 exposures. The data provide evidence that relative lack of NO activity contributes to decreased rCBF under HBO2, but, as exposure time is prolonged, NO production increases and augments rCBF in anticipation of neuronal excitation.

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Aberrant Auditory Steady-State Response of Awake Mice After Single Application of the NMDA Receptor Antagonist MK-801 Into the Medial Geniculate Body

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyaa022 ◽

2020 ◽

Vol 23 (7) ◽

pp. 459-468 ◽

Cited By ~ 2

Author(s):

Xuejiao Wang ◽

Yingzhuo Li ◽

Jingyu Chen ◽

Zijie Li ◽

Jinhong Li ◽

...

Keyword(s):

Prefrontal Cortex ◽

Steady State ◽

Local Field ◽

Local Field Potential ◽

Phase Locking ◽

Field Potential ◽

Medial Geniculate Body ◽

Systemic Administration ◽

Mk 801 ◽

Medial Geniculate

Abstract Background Systemic administration of noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists such as MK-801 is widely used to model psychosis of schizophrenia (SZ). Acute systemic MK-801 in rodents caused an increase of the auditory steady-state responses (ASSRs), the oscillatory neural responses to periodic auditory stimulation, while most studies in patients with SZ reported a decrease of ASSRs. This inconsistency may be attributable to the comprehensive effects of systemic administration of MK-801. Here, we examined how the ASSR is affected by selectively blocking NMDAR in the thalamus. Methods We implanted multiple electrodes in the auditory cortex (AC) and prefrontal cortex to simultaneously record the local field potential and spike activity (SA) of multiple sites from awake mice. Click-trains at a 40-Hz repetition rate were used to evoke the ASSR. We compared the mean trial power and phase-locking factor and the firing rate of SA before and after microinjection of MK-801 (1.5 µg) into the medial geniculate body (MGB). Results We found that both the AC and prefrontal cortex showed a transient local field potential response at the onset of click-train stimulus, which was less affected by the application of MK-801 in the MGB. Following the onset response, the AC also showed a response continuing throughout the stimulus period, corresponding to the ASSR, which was suppressed by the application of MK-801. Conclusion Our data suggest that the MGB is one of the generators of ASSR, and NMDAR hypofunction in the thalamocortical projection may account for the ASSR deficits in SZ.

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Working memory deficits in neuronal nitric oxide synthase knockout mice: Potential impairments in prefrontal cortex mediated cognitive function

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2011.04.097 ◽

2011 ◽

Vol 408 (4) ◽

pp. 707-712 ◽

Cited By ~ 25

Author(s):

Sandra P. Zoubovsky ◽

Vladimir M. Pogorelov ◽

Yu Taniguchi ◽

Sun-Hong Kim ◽

Peter Yoon ◽

...

Keyword(s):

Nitric Oxide ◽

Working Memory ◽

Prefrontal Cortex ◽

Cognitive Function ◽

Nitric Oxide Synthase ◽

Knockout Mice ◽

Neuronal Nitric Oxide Synthase ◽

Memory Deficits ◽

Oxide Synthase

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Differential modulation of the contextual conditioned emotional response by CB1 and TRPV1 receptors in the ventromedial prefrontal cortex: Possible involvement of NMDA/nitric oxide-related mechanisms

Journal of Psychopharmacology ◽

10.1177/0269881120928201 ◽

2020 ◽

Vol 34 (9) ◽

pp. 1043-1055

Author(s):

Daniela L Uliana ◽

Leandro S Antero ◽

Anna B Borges-Assis ◽

Jessica Rosa ◽

Carla Vila-Verde ◽

...

Keyword(s):

Nitric Oxide ◽

Prefrontal Cortex ◽

Emotional Response ◽

Soluble Guanylate Cyclase ◽

Conditioned Emotional Response ◽

Nmda Antagonist ◽

Ventromedial Prefrontal Cortex ◽

Nitric Oxide Synthase Inhibitor ◽

Trpv1 Receptors ◽

Response Expression

Background: Blockade of cannabinoid CB1 or vanilloid TRPV1 receptors in the ventromedial prefrontal cortex of rats respectively increases or decreases the conditioned emotional response during re-exposure to a context previously paired with footshocks. Although these mechanisms are unknown, they may involve local modulation of glutamatergic and nitrergic signaling. Aim: We investigated whether these mechanisms are involved in the reported effects of CB1 and TRPV1 modulation in the ventromedial prefrontal cortex. Methods: Freezing behavior and autonomic parameters were recorded during the conditioned response expression. Results: The CB1 receptors antagonist NIDA, or the TRPV1 agonist capsaicin (CPS) in the ventromedial prefrontal cortex increased the conditioned emotional response expression, and these effects were prevented by TRPV1 and CB1 antagonism, respectively. The increased conditioned emotional response evoked by NIDA and CPS were prevented by an NMDA antagonist or a neuronal nitric oxide synthase inhibitor. A nitric oxide scavenger or a soluble guanylate cyclase inhibitor prevented only the NIDA effects and the CPS effect was prevented by a non-selective antioxidant drug, as nitric oxide can also induce reactive oxygen species production. Conclusion: Our results suggest that CB1 and TRPV1 receptors in the ventromedial prefrontal cortex differently modulate the expression of conditioned emotional response through glutamatergic and nitrergic mechanisms, although different pathways may be involved.

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