title: Perinatal exposure to delta-9-tetrahydrocannabinol causes enduring cognitive deficits associated with alteration of cortical gene expression and neurotransmission in rats.
abstract: The aim of the present study was to investigate whether perinatal exposure to a moderate dose of delta-9-tetrahydrocannabinol (THC) alters cortical gene expression and neurotransmission, leading to enduring cognitive dysfunctions in rat offspring. To this purpose, rat dams were treated, from gestational day 15 to postnatal day 9, with THC at a daily dose (5 mg/kg, per os) devoid of overt signs of toxicity. THC did not influence reproduction parameters, whereas it caused subtle neurofunctional deficits in the adult offspring. Particularly, perinatal THC induced long-lasting alterations of cortical genes related to glutamatergic and noradrenergic systems, associated with a decrease in the cortical extracellular levels of both neurotransmitters. These alterations may account, at least in part, for the enduring cognitive impairment displayed by THC-exposed offspring. Taken together, the present results highlight how exposure to cannabinoids during early stages of brain development can lead to irreversible, subtle dysfunctions in the offspring.
authors.affiliation: Department of Human Physiology and Pharmacology, Sapienza, University of Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Campolongo
authors.forename: Viviana
authors.initials: V
authors.lastname: Trezza
authors.forename: Tommaso
authors.initials: T
authors.lastname: Cassano
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaetani
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Morgese
authors.forename: Massimo
authors.initials: M
authors.lastname: Ubaldi
authors.forename: Laura
authors.initials: L
authors.lastname: Soverchia
authors.forename: Tiziana
authors.initials: T
authors.lastname: Antonelli
authors.forename: Luca
authors.initials: L
authors.lastname: Ferraro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Massi
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccocioppo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cuomo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects; D013759:Dronabinol / Q000633:toxicity*; D005239:Fear / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D005973:Glutamine / Q000235:genetics* / Q000378:metabolism; D007266:Inhibition, Psychological; D011939:Mental Recall / Q000187:drug effects*; D009638:Norepinephrine / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017397:Prefrontal Cortex / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D012153:Retention, Psychology / Q000187:drug effects; D012919:Social Behavior; D009435:Synaptic Transmission / Q000187:drug effects* / Q000235:genetics
chemical_list: D005973:Glutamine; D013759:Dronabinol; D009638:Norepinephrine