Blockade of cannabinoid CB receptor function protects against in vivo disseminating brain damage following NMDA-induced excitotoxicity

H.H. Hansen; J.A. Ramos; J. Fernández-Ruiz; I. Azcoitia; Harald S. Hansen; S. Pons; L.M. García-Segura; J. Romero

doi:10.1046/j.1471-4159.2002.00961.x

Blockade of cannabinoid CB receptor function protects against in vivo disseminating brain damage following NMDA-induced excitotoxicity

H.H. Hansen, J.A. Ramos, J. Fernández-Ruiz, I. Azcoitia, Harald S. Hansen, S. Pons, L.M. García-Segura, J. Romero

74 Citations (Scopus)

Abstract

The ability of cannabinoid CB, receptors to influence glutamatergic excitatory neurotransmission has fueled interest in how these receptors and their endogenous ligands may interact in conditions of excitotoxic insults. The present study characterized the impact of stimulated and inhibited CB receptor function on NMDA-induced excitotoxicity. Neonatal (6-day-old) rat pups received a systemic injection of a mixed CB/CB receptor agonist (WIN55,212-2) or their respective antagonists (SR141716A for CB and SR144528 for CB) prior to an unilateral intrastriatal microinjection of NMDA. The NMDA-induced excitotoxic damage in the ipsilateral forebrain was not influenced by agonist-stimulated CB receptor function. In contrast, blockade of CB, but not CB, receptor activity evoked a robust neuroprotective response by reducing the infarct area and the number of cortical degenerating neurons. These results suggest a critical involvement of CB receptor tonus on neuronal survival following NMDA receptor-induced excitotoxicity in vivo.

Original language	English
Journal	Journal of Neurochemistry
Volume	82
Issue number	1
Pages (from-to)	154-158
Number of pages	5
ISSN	0022-3042
DOIs	https://doi.org/10.1046/j.1471-4159.2002.00961.x
Publication status	Published - 1 Jan 2002

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title = "Blockade of cannabinoid CB receptor function protects against in vivo disseminating brain damage following NMDA-induced excitotoxicity",

abstract = "The ability of cannabinoid CB, receptors to influence glutamatergic excitatory neurotransmission has fueled interest in how these receptors and their endogenous ligands may interact in conditions of excitotoxic insults. The present study characterized the impact of stimulated and inhibited CB receptor function on NMDA-induced excitotoxicity. Neonatal (6-day-old) rat pups received a systemic injection of a mixed CB/CB receptor agonist (WIN55,212-2) or their respective antagonists (SR141716A for CB and SR144528 for CB) prior to an unilateral intrastriatal microinjection of NMDA. The NMDA-induced excitotoxic damage in the ipsilateral forebrain was not influenced by agonist-stimulated CB receptor function. In contrast, blockade of CB, but not CB, receptor activity evoked a robust neuroprotective response by reducing the infarct area and the number of cortical degenerating neurons. These results suggest a critical involvement of CB receptor tonus on neuronal survival following NMDA receptor-induced excitotoxicity in vivo.",

author = "H.H. Hansen and J.A. Ramos and J. Fern{\'a}ndez-Ruiz and I. Azcoitia and Hansen, {Harald S.} and S. Pons and L.M. Garc{\'i}a-Segura and J. Romero",

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AU - Hansen, H.H.

AU - Ramos, J.A.

AU - Fernández-Ruiz, J.

AU - Azcoitia, I.

AU - Hansen, Harald S.

AU - Pons, S.

AU - García-Segura, L.M.

AU - Romero, J.

PY - 2002/1/1

Y1 - 2002/1/1

N2 - The ability of cannabinoid CB, receptors to influence glutamatergic excitatory neurotransmission has fueled interest in how these receptors and their endogenous ligands may interact in conditions of excitotoxic insults. The present study characterized the impact of stimulated and inhibited CB receptor function on NMDA-induced excitotoxicity. Neonatal (6-day-old) rat pups received a systemic injection of a mixed CB/CB receptor agonist (WIN55,212-2) or their respective antagonists (SR141716A for CB and SR144528 for CB) prior to an unilateral intrastriatal microinjection of NMDA. The NMDA-induced excitotoxic damage in the ipsilateral forebrain was not influenced by agonist-stimulated CB receptor function. In contrast, blockade of CB, but not CB, receptor activity evoked a robust neuroprotective response by reducing the infarct area and the number of cortical degenerating neurons. These results suggest a critical involvement of CB receptor tonus on neuronal survival following NMDA receptor-induced excitotoxicity in vivo.

AB - The ability of cannabinoid CB, receptors to influence glutamatergic excitatory neurotransmission has fueled interest in how these receptors and their endogenous ligands may interact in conditions of excitotoxic insults. The present study characterized the impact of stimulated and inhibited CB receptor function on NMDA-induced excitotoxicity. Neonatal (6-day-old) rat pups received a systemic injection of a mixed CB/CB receptor agonist (WIN55,212-2) or their respective antagonists (SR141716A for CB and SR144528 for CB) prior to an unilateral intrastriatal microinjection of NMDA. The NMDA-induced excitotoxic damage in the ipsilateral forebrain was not influenced by agonist-stimulated CB receptor function. In contrast, blockade of CB, but not CB, receptor activity evoked a robust neuroprotective response by reducing the infarct area and the number of cortical degenerating neurons. These results suggest a critical involvement of CB receptor tonus on neuronal survival following NMDA receptor-induced excitotoxicity in vivo.

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Blockade of cannabinoid CB receptor function protects against in vivo disseminating brain damage following NMDA-induced excitotoxicity

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