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Effects of the endogeneous cannabinoid, anandamide, on neuronal activity in rat hippocampal slices
Author(s) -
Ameri Angela,
Wilhelm Alwina,
Simmet Thomas
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702478
Subject(s) - anandamide , postsynaptic potential , cannabinoid , cannabinoid receptor , population spike , chemistry , excitatory postsynaptic potential , neuroscience , population , pharmacology , agonist , inhibitory postsynaptic potential , biology , receptor , medicine , biochemistry , environmental health
The arachidonic acid derivative arachidonylethanolamide (anandamide) is an endogeneous ligand of cannabinoid receptors that induces pharmacological actions similar to those of cannabinoids such as Δ 9 ‐tetrahydrocannabinol (THC). We examined whether anandamide can influence excessive neuronal activity by investigating stimulation‐induced population spikes and epileptiform activity in rat hippocampal slices. For this purpose, the effects of anandamide were compared with those of the synthetic cannabinoid agonist WIN 55,212‐2 and its inactive S(−)‐enantiomer WIN 55,212‐3. Both anandamide (1 and 10 μ M ) and WIN 55,212‐2 (0.1 and 1 μ M ) decreased the amplitude of the postsynaptic population spike and the slope of the field excitatory postsynaptic potential (field e.p.s.p.) without affecting the presynaptic fibre spike of the afferents. At a concentration of 1 μ M , WIN 55,212‐2 completely suppressed the postsynaptic spike, whereas the S(−)‐enantiomer WIN 55,212‐3 produced only a slight depression. The CB 1 receptor antagonist SR 141716 blocked the inhibition evoked by the cannabinoids. SR 141716 had a slight facilitatory effect on neuronal excitability by itself. Anandamide shifted the input‐output curve of the postsynaptic spike and the field e.p.s.p. to the right and increased the magnitude of paired‐pulse facilitation indicating a presynaptic mechanism of action. Anandamide and WIN 55,212‐2, but not WIN 55,212‐3, attenuated both stimulus‐triggered epileptiform activity in CA1 elicited by omission of Mg 2+ and spontaneously occurring epileptiform activity in CA3 elicited by omission of Mg 2+ and elevation of K + to 8 m M . The antiepileptiform effect of these cannabinoids was blocked by SR 141716. In conclusion, cannabinoid receptors of the CB 1 type as well as their endogeneous ligand, anandamide, are involved in the control of neuronal excitability, thus reducing excitatory neurotransmission at a presynaptic site, a mechanism which might be involved in the prevention of excessive excitability leading to epileptiform activity.British Journal of Pharmacology (1999) 126 , 1831–1839; doi: 10.1038/sj.bjp.0702478