am-281 and guvacine

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]-(1-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 degrees C. 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 degrees C. 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 degrees C, but increased paired pulse depression at 35 degrees C. 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.

Topics: Animals; Benzoxazines; Cannabinoids; Female; gamma-Aminobutyric Acid; Hippocampus; In Vitro Techniques; Morpholines; Naphthalenes; Nicotinic Acids; Nipecotic Acids; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptors, Cannabinoid; Receptors, Drug; Synaptic Transmission; Temperature