title: Prenatal exposure to a cannabinoid agonist produces memory deficits linked to dysfunction in hippocampal long-term potentiation and glutamate release.
abstract: To investigate the possible long-term consequences of gestational exposure to cannabinoids on cognitive functions, pregnant rats were administered with the CB1 receptor agonist WIN 55,212-2 (WIN), at a dose (0.5 mgkg) that causes neither malformations nor overt signs of toxicity. Prenatal WIN exposure induced a disruption of memory retention in 40- and 80-day-old offspring subjected to a passive avoidance task. A hyperactive behavior at the ages of 12 and 40 days was also found. The memory impairment caused by the gestational exposure to WIN was correlated with alterations of hippocampal long-term potentiation (LTP) and glutamate release. LTP induced in CA3-CA1 synapses decayed faster in brain slices of rats born from WIN-treated dams, whereas posttetanic and short-term potentiation were similar to the control group. In line with LTP shortening, in vivo microdialysis showed a significant decrease in basal and K(+)-evoked extracellular glutamate levels in the hippocampus of juvenile and adult rats born from WIN-treated dams. A similar reduction in glutamate outflow was also observed in primary cell cultures of hippocampus obtained from pups born from mothers exposed to WIN. The decrease in hippocampal glutamate outflow appears to be the cause of LTP disruption, which in turn might underlie, at least in part, the long-lasting impairment of cognitive functions caused by the gestational exposure to this cannabinoid agonist. These findings could provide an explanation of cognitive alterations observed in children born from women who use marijuana during pregnancy.
authors.affiliation: Department of Experimental Biology, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Mereu
authors.forename: Mauro
authors.initials: M
authors.lastname: Fà
authors.forename: Luca
authors.initials: L
authors.lastname: Ferraro
authors.forename: Raffaele
authors.initials: R
authors.lastname: Cagiano
authors.forename: Tiziana
authors.initials: T
authors.lastname: Antonelli
authors.forename: Maria
authors.initials: M
authors.lastname: Tattoli
authors.forename: Veronica
authors.initials: V
authors.lastname: Ghiglieri
authors.forename: Sergio
authors.initials: S
authors.lastname: Tanganelli
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gessa
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cuomo
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D048588:Benzoxazines; D002478:Cells, Cultured; D004594:Electrophysiology; D005260:Female; D018698:Glutamic Acid / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008385:Marijuana Smoking / Q000009:adverse effects; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D017551:Microdialysis; D009025:Morpholines / Q000008:administration & dosage / Q000633:toxicity; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000008:administration & dosage / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists*
chemical_list: D048588:Benzoxazines; 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