Δ 9-Tetrahydrocannabinol (THC) and AM 404 protect against cerebral ischaemia in gerbils through a mechanism involving cannabinoid and opioid receptors

A. Zani, D. Braida, V. Capurro, M. Sala

Research output: Contribution to journalArticle

Abstract

Background and purpose: It has been suggested that the endocannabinoid system elicits neuroprotection against excitotoxic brain damage. In the present study the therapeutic potential of AM 404 on ischaemia-induced neuronal injury was investigated in vivo and compared with that of the classical cannabinoid receptor type 1 (CB 1) agonist, Δ 9- tetraydrocannabinol (THC), using a model of transient global cerebral ischaemia in the gerbil. Experimental approach: The effects of AM 404 (0.015-2 mg kg -1) and THC (0.05-2 mg kg -1), given 5 min after ischaemia, were measured from 1 h to 7 days in terms of electroencephalographic (EEG) total spectral power, spontaneous motor activity, memory function, rectal temperature and hippocampal CA 1 neuronal count. Key results: Over the dose range tested, AM 404 (2 mg kg -1) and THC (1 mg kg -1) completely reversed the ischaemia-induced behavioural, EEG and histological damage. Only THC (1 and 2 mg kg -1) induced a decrease of body temperature. Pretreatment with the selective CB 1 receptor antagonist, AM 251 (1 mg kg -1) and the opioid antagonist, naloxone (2 mg kg -1) reversed the protective effect induced by both AM 404 and THC while the TRPV 1 vanilloid antagonist, capsazepine (0.01 mg kg -1), was ineffective. Conclusions and implications: Our findings demonstrate that AM 404 and THC reduce neuronal damage caused by bilateral carotid occlusion in gerbils and that this protection is mediated through an interaction with CB 1 and opioid receptors. Endocannabinoids might form the basis for the development of new neuroprotective drugs useful for the treatment of stroke and other neurodegenerative pathologies.

Original languageEnglish
Pages (from-to)1301-1311
Number of pages11
JournalBritish Journal of Pharmacology
Volume152
Issue number8
DOIs
Publication statusPublished - Dec 2007

Keywords

  • (Endo)cannabinoid
  • Electroencephalogram
  • Ischaemia
  • Memory
  • Motor activity
  • Rectal temperature
  • Vanilloid

ASJC Scopus subject areas

  • Pharmacology

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