title: The cannabinoid receptor agonist WIN 55,212-2 regulates glutamate transmission in rat cerebral cortex: an in vivo and in vitro study.
abstract: The effects of the cannabinoid receptor agonist WIN 55,212-2 on endogenous extracellular glutamate levels in the prefrontal cortex of the awake rat and in primary cultures of rat cerebral cortex neurons were investigated. In the prefrontal cortex WIN 55,212-2 (0.1 and 1 mg/kg i.p.) increased dialysate glutamate levels from of the awake rat, while the lower (0.01 mg/kg) and the higher (2 mg/kg) doses were ineffective. Furthermore, the WIN 55,212-2 (0.1 mg/kg)- induced increase of dialysate glutamate levels was counteracted by pretreatment with the selective CB(1) receptor antagonist SR141716A (0.1 mg/kg i.p.) and by the local perfusion with a low-calcium Ringer solution (Ca(2+) 0.2 mM). In primary cultures of rat cerebral cortex neurons, WIN 55,212-2 (0.01--100 nM) increased extracellular glutamate levels, displaying a bell-shaped concentration-response curve. The facilitatory effect of WIN 55,212-2 (1 nM) was fully counteracted by SR141716A (10 nM), by the replacement of the normal Krebs Ringer-bicarbonate buffer with a low Ca(2+) medium (0.2 mM) and by the IP(3) receptor antagonist xestospongin C (1 microM). These in vivo and in vitro findings suggest an increase in cortical glutamatergic transmission by CB(1) receptors, an effect that may underlie some of the psychoactive and behavioural actions of acute exposure to marijuana.
authors.affiliation: Department of Clinical and Experimental Medicine, Pharmacology Section, University of Ferrara, Ferrara, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ferraro
authors.forename: M C
authors.initials: MC
authors.lastname: Tomasini
authors.forename: G L
authors.initials: GL
authors.lastname: Gessa
authors.forename: B W
authors.initials: BW
authors.lastname: Bebe
authors.forename: S
authors.initials: S
authors.lastname: Tanganelli
authors.forename: T
authors.initials: T
authors.lastname: Antonelli
mesh_terms: D000818:Animals; D048588:Benzoxazines; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002186:Cannabinoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003470:Culture Media; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D008297:Male; D017551:Microdialysis; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; 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; D000077285:Rimonabant; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D048588:Benzoxazines; D015220:Calcium Channels; D002186:Cannabinoids; D003470:Culture Media; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D018698:Glutamic Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant; D002118:Calcium