Vaporized Δ9-THC in utero results in reduced birthweight, increased locomotion, and altered wake-cycle activity dependent on dose, sex, and diet in the offspring

Roeder, Nicole M.; Penman, Samantha L.; Richardson, Brittany J.; Wang, Jia; Freeman-Striegel, Lily; Khan, Anas; Pareek, Ojas; Weiss, Maia; Mohr, Patrick; Eiden, Rina D.; Chakraborty, Saptarshi; Thanos, Panayotis K.

doi:10.1016/j.lfs.2024.122447

Cited by 4 publications

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Oral pre‐ and early postnatal cannabis exposure disinhibits ventral tegmental area dopamine neuron activity but does not influence cocaine preference in offspring in mice

Peterson,

Baglot,

Sallam

et al. 2024

J of Neuroscience Research

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Cannabis consumption has increased from 1.5% to 2.5% in Canada between 2012 and 2019. Clinical studies have indicated effects of prenatal cannabis exposure on birth weight, substance use, and neurodevelopmental disorders, but are confounded by several difficult to control variables. Animal models allow for examination of the mechanism of cannabis‐induced changes in neurodevelopment and behavior, while controlling dose and timing. Several animal models of prenatal cannabis exposure exist which provide varying levels of construct validity, control of dose, and exposure to maternal stress. Using a voluntary oral consumption model, mouse dams received 5 mg/kg Δ9‐tetrahydrocannabinol (THC) whole cannabis oil in peanut butter daily from gestational day 1 (GD1) to postnatal day 10 (PD10). At GD1, GD18, PD1, PD10, and PD15, maternal plasma was collected; pup brains were collected from GD18 onward. Pup brains had higher levels of THC and cannabidiol at each time point, each of which persisted in maternal plasma and pup brains past the end of treatment (PD15). Male and female adolescent offspring were examined for changes to ventral tegmental area (VTA) dopamine neuron activity and cocaine‐seeking behavior. Prenatal and early postnatal (GD1–PD10) cannabis‐exposed male, but not female mice had decreased gamma‐aminobutyric acid (GABAergic) input, depolarized resting membrane potential, and increased spontaneous firing of VTA dopamine neurons. Cannabis‐exposed offspring showed faster decay of N‐methyl‐D‐aspartate (NMDA) currents in both sexes. However, no differences in cocaine‐seeking behavior were noted. These data characterize a voluntary prenatal cannabis exposure model and demonstrates VTA dopamine neuronal activity is disinhibited in offspring.

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