Effects of Win 55,212-2 on hippocampal CA1 long-term potentiation in experiments controlled for basal glutamatergic synaptic transmission.
Cannabinoids, the active components of marijuana, are presumed to affect memory by an action on long-term potentiation. However, these molecules also reduce hippocampal glutamatergic neurotransmission. To distinguish the two activities, we studied the effects of the synthetic cannabinoid (R)-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphtalenylmethanone (Win 55,212-2, 10 microM) on CA1 hippocampal responses generated by the activation of two independent pathways, one of which was potentiated with a tetanic stimulation. The results of the study show the following: (a) the drug does not affect long-term potentiation provided that the responses are compared to those obtained in the unpotentiated control pathway; (b) Win 55,212-2 increases post-tetanic potentiation.
Diana
Giovanni
G
Istituto Superiore di Sanita, Laboratory of Pharmacology, Viale Regina Elena 299, 00161, Rome, Italy. giovanni.diana@iss.it
Pieri
Massimo
M
Valentini
Giovanni
G
D000818:Animals; D048588:Benzoxazines; D002186:Cannabinoids / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; 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