Effects of cannabis exposure in the prenatal and adolescent periods: Preclinical and clinical studies in both sexes

Tirado-Muñoz, Judith; López-Rodríguez, Ana Belén; Fonseca, Francina; Farré, Magı́; Viveros, María-Paz

doi:10.1016/j.yfrne.2020.100841

Cited by 32 publications

(28 citation statements)

References 180 publications

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“…Evidence suggests a sex bias in response to PCE 6–8 . In particular, we found that male PCE rats display a psychotic-like phenotype in response to acute THC or stress, a higher sensitivity to a dopamine D2 agonist and engage in risk taking behaviors 34,37 .…”

Section: Resultsmentioning

confidence: 99%

“…Children with a parent who has a mental illness or substance use disorder have a higher risk of psychiatric problems themselves 4,5 . Critically, prenatal cannabis exposure (PCE) increases the risk for child psychopathology, ranging from affective symptoms to ADHD and psychotic-like experiences 6–11 . With recreational cannabis legalization and permissive sociocultural attitudes expanding worldwide, and the use of cannabis among pregnant women on a sharp rise 12–14 , concern increases over the long-term negative impact on next generation health (i.e., pediatric concern) 15–19 .…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, PCE is thought to act as a “first hit” on neurodevelopmental trajectories 24 . Of note, a sex bias in response to PCE is well recognized 6–8 . However, the underlying mechanisms are not sufficiently studied also because causal inference is difficult to be established in population studies.…”

Section: Introductionmentioning

confidence: 99%

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Prenatal THC does not affect female mesolimbic dopaminergic system in preadolescent rats

Traccis

Serra

Sagheddu

et al. 2020

Preprint

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Cannabis use among pregnant women is increasing worldwide along with permissive sociocultural attitudes towards it. Prenatal cannabis exposure (PCE), however, is associated with adverse outcome among offspring ranging from reduced birth weight to child psychopathology. We have previously shown that male rat offspring prenatally exposed to Δ9-tetrahydrocannabinol (THC), a rat model of PCE, exhibit extensive molecular, cellular and synaptic changes in dopamine neurons of the ventral tegmental area (VTA), resulting in a susceptible mesolimbic dopamine system associated with a psychotic-like endophenotype. This phenotype only reveals itself upon a single exposure to THC in males but not females. Here, we characterized the impact of PCE on female behaviors and mesolimbic dopamine system function by combining in vivo single-unit extracellular recordings in anesthetized animals and ex vivo patch clamp recordings, along with neurochemical and behavioral analyses. We find that PCE female offspring do not show any spontaneous or THC-induced behavioral disease-relevant phenotypes. The THC-induced increase of dopamine levels in nucleus accumbens was reduced in PCE female offspring, even when VTA dopamine activity in vivo and ex vivo did not differ compared to control. These findings indicate that PCE impacts mesolimbic dopamine function and its related-behavioral domains in a sex-dependent manner and warrant further investigations to decipher the mechanisms determining this sex-related protective effect from intrauterine THC exposure.HighlightsPCE female offspring do not manifest a disease-relevant phenotypePrenatal THC does not affect female dopaminergic neuronsPCE female mesolimbic dopamine function is less responsive to acute THC

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prenatal THC does not affect female mesolimbic dopaminergic system in preadolescent rats

Traccis

Serra

Sagheddu

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Children with a parent who has a mental illness or substance use disorder have a higher risk of psychiatric problems themselves [4,5]. Critically, prenatal cannabis exposure (PCE) increases the risk for child psychopathology, ranging from affective symptoms to attention deficit hyperactive disorder (ADHD) and psychotic-like experiences [6][7][8][9][10][11]. With recreational cannabis legalization and permissive sociocultural attitudes expanding worldwide, and the use of cannabis among pregnant women on a sharp rise [12][13][14], concern has increased over the long-term negative impact on next-generation health (i.e., pediatric concern) [15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Prenatal THC Does Not Affect Female Mesolimbic Dopaminergic System in Preadolescent Rats

Traccis

Serra

Sagheddu

et al. 2021

IJMS

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Cannabis use among pregnant women is increasing worldwide along with permissive sociocultural attitudes toward it. Prenatal cannabis exposure (PCE), however, is associated with adverse outcome among offspring, ranging from reduced birth weight to child psychopathology. We have previously shown that male rat offspring prenatally exposed to Δ9-tetrahydrocannabinol (THC), a rat model of PCE, exhibit extensive molecular, cellular, and synaptic changes in dopamine neurons of the ventral tegmental area (VTA), resulting in a susceptible mesolimbic dopamine system associated with a psychotic-like endophenotype. This phenotype only reveals itself upon a single exposure to THC in males but not females. Here, we characterized the impact of PCE on female behaviors and mesolimbic dopamine system function by combining in vivo single-unit extracellular recordings in anesthetized animals and ex vivo patch clamp recordings, along with neurochemical and behavioral analyses. We find that PCE female offspring do not show any spontaneous or THC-induced behavioral disease-relevant phenotypes. The THC-induced increase in dopamine levels in nucleus accumbens was reduced in PCE female offspring, even when VTA dopamine activity in vivo and ex vivo did not differ compared to control. These findings indicate that PCE impacts mesolimbic dopamine function and its related behavioral domains in a sex-dependent manner and warrant further investigations to decipher the mechanisms determining this sex-related protective effect from intrauterine THC exposure.

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“…No effect on long-term physical growth and timing of pubertal milestones Diminished scores on tests of academic achievement (Goldschmidt, Richardson, Willford, Severtson, & Day, 2012) Higher rates of juvenile delinquency (Day et al, 2011) Subtle impairments in attention, working memory and inhibitory control suggest diminished executive functioning skills (Fried et al, 2003;Fried & Smith, 2001;Smith et al, 2016) changes in cognition and social interactions (for reviews see Grant, Petroff, Isoherranen, Stella, & Burbacher, 2018;Scheyer et al, 2019;Tirado-Muñoz et al, 2020). No congenital anomalies were described in infant rhesus monkeys exposed to THC in-utero during the second and third trimester (Asch & Smith, 1986).…”

Section: Messages From Research With Animal Modelsmentioning

confidence: 99%

Update on the developmental consequences of cannabis use during pregnancy and lactation

Grant

Conover

Chambers

2020

Birth Defects Research

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There is a strong increase in prevalence trends for cannabis use during pregnancy and lactation as more states legalize use of this drug. Information on the teratogenic risk of cannabis is limited but some important themes can be gleaned. Studies have not found a unique phenotypic signature of prenatal exposure but an increased risk of congenital anomalies, particularly gastroschisis, has been reported. Changes in fetal growth have been described in some epidemiological studies but long‐term patterns of physical growth appear unaffected. Prenatal exposure to cannabis is not generally associated with reductions in global IQ but specific cognitive skills, especially attention and memory, can be negatively impacted. Long‐term impacts on psychological health include increased rates of depressive symptoms and anxiety as well as delinquency. Relatively little is known about the risk of maternal cannabis use during lactation but data suggest that infant exposure is relatively low compared to maternal exposure. As delta‐9‐tetrahydrocannabinol (THC) levels increase to meet consumer demand and routes of exposure diversify, there is a strong need for prospective birth‐cohort studies that collect biological samples to quantify exposure. Data from such studies will be critical to overcoming the weaknesses of past cannabis research and are essential to establishing reliable information on the risks of maternal use. Until that time, health care providers should be encouraged to talk about the risks and benefits associated with cannabis use during pregnancy and lactation with their patients, emphasizing that fetal and neonatal risks cannot be excluded at this time.

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Effects of cannabis exposure in the prenatal and adolescent periods: Preclinical and clinical studies in both sexes

Cited by 32 publications

References 180 publications

Prenatal THC does not affect female mesolimbic dopaminergic system in preadolescent rats

Prenatal THC does not affect female mesolimbic dopaminergic system in preadolescent rats

Prenatal THC Does Not Affect Female Mesolimbic Dopaminergic System in Preadolescent Rats

Update on the developmental consequences of cannabis use during pregnancy and lactation

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