Long-term effects on cortical glutamate release induced by prenatal exposure to the cannabinoid receptor agonist (r)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone: an in vivo microdialysis study in the awake rat

Antonelli, Tiziana; Tanganelli, Sergio; Tomasini, Maria Cristina; Finetti, Simone; Trabace, Luigia; Steardo, Luca; Sabino, Valentina; Carratù, M.R.; Cuomo, V.; Ferraro, Luca

doi:10.1016/j.neuroscience.2003.10.034

Cited by 44 publications

(36 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The low expression of EAAC1 in the cerebella of 20-day-old THC-exposed animals might, therefore, also reflect impaired maturation of glutamatergic cerebellar neurons, which could lead to impaired motor coordination, since it has been suggested that the cerebellum may be involved in the motor effects of cannabinoids [Breivogel and Childers, 1998]. An interesting aspect derived from the present observations is that these glutamatergic alterations produced by THC during development might result in long-term alterations in several cognitive and memory processes regulated by glutamate in adult rats, as several studies have recently documented [Mereu et al, 2003;Antonelli et al, 2004]. It is also important to note that glutamate, as happens with other neurotransmitters such as dopamine or serotonin [Levitt et al, 1997], might also play a neurotrophic role during the ontogenetic period, thus influencing the maturation of glutamatergic pathways themselves or other neurotransmitters and then producing profound behavioral disturbances.…”

Section: Discussionmentioning

confidence: 60%

Prenatal Cannabinoid Exposure Down- Regulates Glutamate Transporter Expressions (GLAST and EAAC1) in the Rat Cerebellum

et al. 2004

View full text Add to dashboard Cite

Efficient reuptake of synaptically released glutamate is essential for preventing glutamate receptor overstimulation and neuronal death. Glutamate transporters play a vital role in removing extracellular glutamate from the synaptic cleft. This study analyzed the expression of the glial (GLAST) and neuronal (EAAC1) subtypes of glutamate transporter in the cerebellum of male and female offspring exposed pre- and postnatally to Δ⁹-tetrahydrocannabinol (THC, the main component of marijuana). Pregnant rats were administered saline or THC from gestational day 5 to postnatal day 20 (PD20). The expression of glutamate transporters was examined at PD20, PD30 and PD70 (10 and 50 days after THC withdrawal) to analyze the short- and long-term effects of prenatal THC exposure. The expression of the glutamate transporter GLAST in astroglial cells and EAAC1 in Purkinje neurons decreased in THC-exposed offspring compared to controls. This reduction was observed at all ages but mainly in males. Moreover, the glial glutamate transporter level in THC-exposed rats (quantified by Western blot) was lower than in control rats. These results suggest that THC exposure during cerebellar development may alter the glutamatergic system not only during the period of drug exposure but in the postnatal stage following withdrawal. The down-regulation reported here might reflect an abnormal maturation of the glutamatergic neuron-glia circuitry.

show abstract

Section: Discussionmentioning

confidence: 60%

Prenatal Cannabinoid Exposure Down- Regulates Glutamate Transporter Expressions (GLAST and EAAC1) in the Rat Cerebellum

et al. 2004

View full text Add to dashboard Cite

show abstract

“…; Antonelli et al . , ). Failure in specification or migration of pyramidal neurons and interneurons could lead to an abnormal distribution into the cerebral cortex and could result in a disturbance of neuronal activity that in turn would be followed by a neurochemical unbalance.…”

Section: Discussionmentioning

confidence: 99%

Prenatal exposure to the CB₁ and CB₂ cannabinoid receptor agonist WIN 55,212‐2 alters migration of early‐born glutamatergic neurons and GABAergic interneurons in the rat cerebral cortex

Saez

Aronne

Caltana

et al. 2014

Journal of Neurochemistry

View full text Add to dashboard Cite

The endocannabinoid system, composed of cannabinoid receptors, endocannabinoids, and synthesis and degradation enzymes, is present since early stages of brain development. During this period, the endocannabinoid system is involved in the regulation of neural progenitor proliferation and specification as well as the migration and differentiation of pyramidal neurons and interneurons. Marijuana consumption during pregnancy represents a serious risk in relation to the fetal brain development since D 9 -tetrahidrocannabinol, the main active compound of cannabis, can reach the fetus through placenta and hemato-encephalic barrier. Cohort studies performed on children and adolescents of mothers who consumed marijuana during pregnancy reported cognitive and comportamental abnormalities. In the present study, we examined the expression of the cannabinoid receptor CB 1 R during corticogenesis in radially and tangentially migrating post-mitotic neurons. We found that prenatal exposure to WIN impaired tangential and radial migration of post-mitotic neurons in the dorsal pallium. In addition, we described alterations of two transcription factors associated with proliferating and newly post-mitotic glutamatergic cells in the dorsal pallium, Tbr1 and Tbr2, and disruption in the number of Cajal-Retzius cells. The present results contribute to the knowledge of neurobiological substrates that determine neuro-comportamental changes that will persist through post-natal life.

show abstract

“…The decrease in hippocampal glutamate overflow was suggested to be the cause of long-term potentiation disruption, which could underlie, in turn, the long-lasting impairment of cognitive functions caused by the gestational exposure to the cannabinoid receptor agonist (Mereu et al 2003). To further support the hypothesis that changes in glutamatergic neurotransmission might be responsible of the cognitive impairment observed in WIN55,212-2-exposed adult offspring, in vivo microdialysis experiments showed that gestational exposure to this cannabinoid receptor agonist induces a consistent reduction of basal and K + -evoked glutamate outflow in the prefrontal cortex of the adult offspring (Antonelli et al 2004). As for the clinical relevance of these preclinical studies, it is important to estimate, by extrapolation, whether the dose of the synthetic cannabinoid agonist compares with that of THC absorbed by cannabis users.…”

Section: Long-term Behavioral Consequences Of Maternal Cannabis Exposurementioning

confidence: 99%

Developmental consequences of perinatal cannabis exposure: behavioral and neuroendocrine effects in adult rodents

et al. 2010

View full text Add to dashboard Cite

RationaleCannabis is the most commonly used illicit drug among pregnant women. Since the endocannabinoid system plays a crucial role in brain development, maternal exposure to cannabis derivatives might result in long-lasting neurobehavioral abnormalities in the exposed offspring. It is difficult to detect these effects, and their underlying neurobiological mechanisms, in clinical cohorts, because of their intrinsic methodological and interpretative issues.ObjectivesThe present paper reviews relevant rodent studies examining the long-term behavioral consequences of exposure to cannabinoid compounds during pregnancy and/or lactation.ResultsMaternal exposure to even low doses of cannabinoid compounds results in atypical locomotor activity, cognitive impairments, altered emotional behavior, and enhanced sensitivity to drugs of abuse in the adult rodent offspring. Some of the observed behavioral abnormalities might be related to alterations in stress hormone levels induced by maternal cannabis exposure.ConclusionsThere is increasing evidence from animal studies showing that cannabinoid drugs are neuroteratogens which induce enduring neurobehavioral abnormalities in the exposed offspring. Several preclinical findings reviewed in this paper are in line with clinical studies reporting hyperactivity, cognitive impairments and altered emotionality in humans exposed in utero to cannabis. Conversely, genetic, environmental and social factors could also influence the neurobiological effects of early cannabis exposure in humans.

show abstract

Long-term effects on cortical glutamate release induced by prenatal exposure to the cannabinoid receptor agonist (r)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone: an in vivo microdialysis study in the awake rat

Cited by 44 publications

References 52 publications

Prenatal Cannabinoid Exposure Down- Regulates Glutamate Transporter Expressions (GLAST and EAAC1) in the Rat Cerebellum

Prenatal Cannabinoid Exposure Down- Regulates Glutamate Transporter Expressions (GLAST and EAAC1) in the Rat Cerebellum

Prenatal exposure to the CB₁ and CB₂ cannabinoid receptor agonist WIN 55,212‐2 alters migration of early‐born glutamatergic neurons and GABAergic interneurons in the rat cerebral cortex

Developmental consequences of perinatal cannabis exposure: behavioral and neuroendocrine effects in adult rodents

Contact Info

Product

Resources

About

Long-term effects on cortical glutamate release induced by prenatal exposure to the cannabinoid receptor agonist (r)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone: an in vivo microdialysis study in the awake rat

Cited by 44 publications

References 52 publications

Prenatal Cannabinoid Exposure Down- Regulates Glutamate Transporter Expressions (GLAST and EAAC1) in the Rat Cerebellum

Prenatal Cannabinoid Exposure Down- Regulates Glutamate Transporter Expressions (GLAST and EAAC1) in the Rat Cerebellum

Prenatal exposure to the CB1 and CB2 cannabinoid receptor agonist WIN 55,212‐2 alters migration of early‐born glutamatergic neurons and GABAergic interneurons in the rat cerebral cortex

Developmental consequences of perinatal cannabis exposure: behavioral and neuroendocrine effects in adult rodents

Contact Info

Product

Resources

About

Prenatal exposure to the CB₁ and CB₂ cannabinoid receptor agonist WIN 55,212‐2 alters migration of early‐born glutamatergic neurons and GABAergic interneurons in the rat cerebral cortex