Abstract
We have previously reported that the synthetic cannabinoid R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(I-naphthalenyl)methanone mesylate (WIN55,212-2) causes a selective inhibition of paired pulse depression of population spikes recorded from the CA1 region of rat hippocampal slices maintained at 28-30 degreesC. We now show that this effect is highly temperature-dependent and that WIN55,212-2 actually increases paired pulse depression of population spikes recorded from slices maintained at 35 degreesC. This temperature dependence was found to correlate with the effects of the known gamma-amino butyric acid (GABA)-uptake inhibitors, nipecotic acid and guvacine, which were without effect at 28-30 degreesC, but increased paired pulse depression at 35 degreesC. The results show that the effects of cannabinoids on synaptic transmission in the hippocampal slice are highly temperature-dependent and it is suggested that this is due to the presence of increased GABA uptake at higher temperatures. (C) 2002 Elsevier Science B.V. All rights reserved.
Original language | English |
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Pages (from-to) | 47-54 |
Number of pages | 7 |
Journal | European Journal of Pharmacology |
Volume | 442 |
Issue number | 1-2 |
DOIs | |
Publication status | Published - 2002 |
Keywords
- WIN55,212-2
- cannabinoid
- hippocampus
- temperature
- GABA (gamma-aminobutyric acid), uptake
- PAIRED-PULSE DEPRESSION
- LONG-TERM POTENTIATION
- IN-VITRO
- NEUROTRANSMITTER UPTAKE
- MEMBRANE-PROPERTIES
- BRAIN SYNAPTOSOMES
- GABA(A) RECEPTORS
- PYRAMIDAL CELLS
- CB1 RECEPTORS
- NEURONS