title: Cross-generational THC exposure alters the developmental sensitivity of ventral and dorsal striatal gene expression in male and female offspring.
abstract: Cannabis (Cannabis sativa, Cannabis indica) is the illicit drug most frequently abused by young men and women. The growing use of the drug has raised attention not only on the impact of direct exposure on the developing brain and behavior later in life, but also on potential cross-generational consequences. Our previous work demonstrated that adolescent exposure to Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, affects reward-related behavior and striatal gene expression in male offspring that were unexposed to the drug during their own lifespan. The significant sex differences documented for most addiction and psychiatric disorders suggest that understanding the perturbation of the brain in the two sexes due to cannabis could provide insights about neuronal systems underpinning vulnerability to psychiatric illnesses. In the current study, we expanded our previous observations in males by analyzing the female brain for specific aberrations associated with cross-generational THC exposure. Based on the impact of adolescent development on subsequent adult behavioral pathology, we examined molecular patterns during both adolescence and adulthood. The results revealed a switch from the ventral striatum during adolescence to the dorsal striatum in adulthood in alterations of gene expression related to synaptic plasticity in both sexes. Females, however, exhibited stronger correlation patterns between genes and also showed locomotor disturbances not evident in males. Overall, the findings demonstrate cross-generational consequences of parental THC exposure in both male and female offspring.
authors.affiliation: Friedman Brain Institute, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Henrietta
authors.initials: H
authors.lastname: Szutorisz
authors.affiliation: Friedman Brain Institute, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Friedman Brain Institute, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Gabor
authors.initials: G
authors.lastname: Egervári
authors.affiliation: Friedman Brain Institute, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: James
authors.initials: J
authors.lastname: Sperry
authors.affiliation: Friedman Brain Institute, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jenna M
authors.initials: JM
authors.lastname: Carter
authors.affiliation: Friedman Brain Institute, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Friedman Brain Institute, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: yasmin.hurd@mssm.edu.
authors.forename: Yasmin L
authors.initials: YL
authors.lastname: Hurd
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000254:growth & development* / Q000378:metabolism*; D013759:Dronabinol / Q000008:administration & dosage*; D005106:Exploratory Behavior; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure; D009473:Neuronal Plasticity; D018812:Paternal Exposure; D012333:RNA, Messenger / Q000378:metabolism; D020318:Rats, Long-Evans
chemical_list: D012333:RNA, Messenger; D013759:Dronabinol
keywords: Cross-generational transmission; Development; Gender; Marijuana; Striatum; Synaptic plasticity