Frequent low-impact exposure to THC during adolescence causes persistent sexually dimorphic alterations in the response to viral infection in mice

Lee, Hye-Lim; Squire, Erica; Fotio, Yannick; Mabou Tagne, Alex; Lee, Jungyeon; Yoon, John Jeongwoo; Hong, Yedam; Kim, Laura Hyunseo; Jung, Kwang-Mook; Piomelli, Daniele

doi:10.1016/j.phrs.2023.107049

Cited by 3 publications

(1 citation statement)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This hypothesis does not rule out the possible contributions made by other organ systems that participate in energy metabolism, such as skeletal muscle and the brain, which may be affected by adolescent THC exposure. Indeed, our own work has found significant transcriptional changes, in both the muscle and brain of mice exposed to THC in adolescence [ 52 , 58 ], which deserve further investigation.…”

Section: Discussionmentioning

confidence: 99%

Overactivation of the Endocannabinoid System in Adolescence Disrupts Adult Adipose Organ Function in Mice

Jung,

Lin,

Piomelli

2024

Cells

Self Cite

View full text Add to dashboard Cite

Cannabis use stimulates calorie intake, but epidemiological studies show that people who regularly use it are leaner than those who don’t. Two explanations have been proposed for this paradoxical finding. One posits that Δ9-tetrahydrocannabinol (THC) in cannabis desensitizes adipose CB1 cannabinoid receptors, stopping their stimulating effects on lipogenesis and adipogenesis. Another explanation is that THC exposure in adolescence, when habitual cannabis use typically starts, produces lasting changes in the developing adipose organ, which impacts adult systemic energy use. Here, we consider these possibilities in the light of a study which showed that daily THC administration in adolescent mice produces an adult metabolic phenotype characterized by reduced fat mass, partial resistance to obesity and dyslipidemia, and impaired thermogenesis and lipolysis. The phenotype, whose development requires activation of CB1 receptors in differentiated adipocytes, is associated with overexpression of myocyte proteins in the adipose organ with unchanged CB1 expression. We propose that adolescent exposure to THC causes lasting adipocyte dysfunction and the consequent emergence of a metabolic state that only superficially resembles healthy leanness. A corollary of this hypothesis, which should be addressed in future studies, is that CB1 receptors and their endocannabinoid ligands may contribute to the maintenance of adipocyte differentiation during adolescence.

show abstract

Section: Discussionmentioning

confidence: 99%

Overactivation of the Endocannabinoid System in Adolescence Disrupts Adult Adipose Organ Function in Mice

Jung,

Lin,

Piomelli

2024

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats

Martinez,

Alizo Vera,

Ruiz

et al. 2024

Preprint

View full text Add to dashboard Cite

Adolescent use of cannabis is linked to later-life changes in cognition, learning, and memory. Rodent models suggest this could be a causal effect of Δ9-tetrahydrocannabinol (THC) influencing the development of circuits underlying these processes, especially for the prefrontal cortex (PFC) which undergoes maturation during adolescence. Here we examined how two weeks of daily exposure to THC (5mg/kg IP) during adolescence persistently impacts cognitive processes involving mPFC dopamine. In male and female Long Evans rats treated in adolescence with THC or vehicle, we quantify acquisition of, and stable performance in two mPFC dopamine-dependent cognitive tasks—attentional set shifting and probability-based reward discounting. We also determined how acute pharmacological or chemogenetic augmentation of dopamine signaling impacts cognition in both groups and both sexes. We found that adolescent THC (AdoTHC) sex-dependently impacts acquisition of cue-guided instrumental reward seeking, but has minimal effects on set-shifting or probability discounting in either sex. When we challenged dopamine circuits by acutely potentiating monoamine signaling with amphetamine (0, 0.25, 0.5 mg/kg) during probability discounting, we confirmed prior findings that amphetamine reduced discounting of improbable reward options, and further showed that this amphetamine effect was more robust in rats with a history of adolescent THC. We next asked whether this potentiated effect of amphetamine involves AdoTHC impacts on dopamine circuits in particular, by attempting to recapitulate the amphetamine effect using more specific chemogenetic stimulation of VTA dopamine neurons. In contrast, we found that neither acute chemogenetic stimulation of VTA dopamine neurons (using a Cre-dependent DREADD in tyrosine hydroxylase:Cre rats), nor pathway-specific chemogenetic stimulation of these neurons' projection to mPFC in particular impacted probability discounting, suggesting that AdoTHC's potentiation of amphetamine effects may reflect alterations of non-VTA dopamine neurons influenced by amphetamine. Results confirm the marked specificity in the cognitive processes impacted by adolescent THC exposure, and suggest that some persistent effects of adolescent THC may alter cognitive responses to amphetamine in a manner independent of VTA dopamine projections to mPFC.

show abstract

Vortioxetine improved schizophrenia‐like behavioral deficits in a Poly I:C‐induced maternal immune activation model of schizophrenia in rats

Taskiran,

Yildiz Taskiran,

Unal

et al. 2024

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

BackgroundSeveral studies provide clear evidence that exposure to various infections during pregnancy are linked with an increased risk for schizophrenia. In preclinical studies, administration of polyinosinic‐polycytidylic acid (Poly I:C) in pregnant rodents can induce maternal immune activation leading to impairments in brain function in the offspring.ObjectivesThe aim of this study was to investigate the effect of vortioxetine, a multimodal selective serotonin reuptake inhibitor (SSRI), in the pathophysiology of Poly I:C‐induced schizophrenia‐like model in rats.MethodsFor this purpose, Poly I:C (8 mg/kg, ip) was injected into pregnant animals 14 days after mating, and tail blood was taken for determination of IL‐6 levels after 2 h. At postnatal days 83–86, behavioral tests were performed.ResultsOur results revealed that Poly I:C caused impairments in prepulse inhibition, novel object recognition, social interaction, and open‐field tests. Chronic administration of vortioxetine (2.5, 5, and 10 mg/kg, ip, postnatal days 69–83) caused significant improvements in these deficits.ConclusionOverall, our findings indicate that vortioxetine may provide new therapeutic approaches for the treatment of schizophrenia. We think that increased serotonergic activity in frontal brain regions may provide the ameliorative effect of vortioxetine, especially on negative and cognitive symptoms. Therefore, it will be useful to determine the efficacy of vortioxetine with combined drugs with further studies.

show abstract

Frequent low-impact exposure to THC during adolescence causes persistent sexually dimorphic alterations in the response to viral infection in mice

Cited by 3 publications

References 52 publications

Overactivation of the Endocannabinoid System in Adolescence Disrupts Adult Adipose Organ Function in Mice

Overactivation of the Endocannabinoid System in Adolescence Disrupts Adult Adipose Organ Function in Mice

Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats

Vortioxetine improved schizophrenia‐like behavioral deficits in a Poly I:C‐induced maternal immune activation model of schizophrenia in rats

Contact Info

Product

Resources

About