Delta(9)-tetrahydrocannabinol increases endogenous extracellular glutamate levels in primary cultures of rat cerebral cortex neurons: involvement of CB(1) receptors.
The effects of the principal psychoactive component of marijuana, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), on endogenous extracellular glutamate levels in primary cultures of rat cerebral cortex neurons were investigated. Locally applied Delta(9)-THC (0.03, 3, 300, and 1,000 nM) concentration-dependently increased basal extracellular glutamate levels (+18% +/- 11%, +54% +/- 10%, +90% +/- 14%, +149% +/- 33% vs. basal). The facilitatory effects of Delta(9)-THC (3 and 300 nM) on cortical glutamate were fully counteracted in the presence of the selective CB(1) receptor antagonist SR141716A (10 nM) and by replacement of the normal Krebs-Ringer bicarbonate buffer with a low-Ca(2+) (0.2 mM) medium. Delta(9)-THC application also induced an enhancement in K(+)-evoked glutamate levels. These findings suggest that an increase in cortical glutamatergic transmission mediated by local CB(1) receptor activation may underlie some of the psychoactive and behavioral effects of acute marijuana consumption.
Tomasini
Maria Cristina
MC
Department of Clinical and Experimental Medicine, Pharmacology Section, University of Ferrara, Ferrara, Italy.
Ferraro
Luca
L
Bebe
Berta Wonjie
BW
Tanganelli
Sergio
S
Cassano
Tommaso
T
Cuomo
Vincenzo
V
Antonelli
Tiziana
T
D000818:Animals; D018929:Cell Culture Techniques; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D013759:Dronabinol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D000077285:Rimonabant
D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D018698:Glutamic Acid; D013759:Dronabinol; D000077285:Rimonabant