Effects of chronic exposure to low doses of Δ9- tetrahydrocannabinol in adolescence and adulthood on serotonin/norepinephrine neurotransmission and emotional behaviors

青少年和成年期长期接触低剂量 Δ9-四氢大麻酚对血清素/去甲肾上腺素神经传递和情绪行为的影响

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作者:Danilo De Gregorio, Joshua Dean Conway, Martha-Lopez Canul, Luca Posa, Francis Rodriguez Bambico, Gabriella Gobbi

Aims

Little is known about the impact of the long-term effects of chronic exposure to low doses of THC in adolescent compared to adult rodents.

Background

Chronic exposure to the Δ9-tetrahydrocannabinol (THC), the main cannabis pharmacological component, during adolescence has been shown to be associated with an increased risk of depression and suicidality in humans. Aims: Little is known about the impact of the long-term effects of chronic exposure to low doses of THC in adolescent compared to adult rodents.

Conclusions

Altogether, these findings suggest that low doses of chronic THC exposure during the developmental period and adulthood could result in increased vulnerability of the 5-HT system and anxiety symptoms; however, depressive phenotypes occur only after adolescent, but not adult exposure, underscoring the higher vulnerability of young ages to the mental effects of cannabis.

Methods

THC (1mg/kg i.p., once a day) or vehicle was administered for 20 days in both adolescent (post-natal day, PND 30-50) and young adult rats (PND 50-70). After a long washout period (20 days), several behavioral paradigms and electrophysiological recordings of serotonin (5-HT) and norepinephrine (NE) neurons were carried out.

Results

Adolescent THC exposure resulted in depressive lbehaviors: a significant decrease in latency to first immobility in the forced swim test, increased anhedonia in the sucrose preference test. Decrease entries in the open arm were observed in the elevated plus maze after adolescent and adult exposure, indicating anxiousphenotype. A significant reduction in dorsal raphe serotonergic neural activity without changing locus coeruleus noradrenergic neural activity was found in THC adolescent and adult exposure. Conclusions: Altogether, these findings suggest that low doses of chronic THC exposure during the developmental period and adulthood could result in increased vulnerability of the 5-HT system and anxiety symptoms; however, depressive phenotypes occur only after adolescent, but not adult exposure, underscoring the higher vulnerability of young ages to the mental effects of cannabis.

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