Perinatal exposure to delta-9-tetrahydrocannabinol causes enduring cognitive deficits associated with alteration of cortical gene expression and neurotransmission in rats.
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.
Campolongo
Patrizia
P
Department of Human Physiology and Pharmacology, Sapienza, University of Rome, Italy.
Trezza
Viviana
V
Cassano
Tommaso
T
Gaetani
Silvana
S
Morgese
Maria Grazia
MG
Ubaldi
Massimo
M
Soverchia
Laura
L
Antonelli
Tiziana
T
Ferraro
Luca
L
Massi
Maurizio
M
Ciccocioppo
Roberto
R
Cuomo
Vincenzo
V
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
D005973:Glutamine; D013759:Dronabinol; D009638:Norepinephrine