6533b822fe1ef96bd127d785
RESEARCH PRODUCT
Prenatal exposure to the CB1 receptor agonist WIN 55,212-2 causes learning disruption associated with impaired cortical NMDA receptor function and emotional reactivity changes in rat offspring
Elisa MazzoniMaria Cristina TomasiniSimone FinettiTommaso CassanoLuca FerraroMaria TattoliSergio TanganelliVincenzo CuomoLuigia TrabaceLuca SteardoTiziana Antonellisubject
MaleMarijuana AbuseCannabinoid receptoractive avoidance behaviour; basal and K+-evoked glutamate levels; cortical cell cultures; homing behaviour; maternal marijuana consumption; ultrasonic vocalizationEmotionsReceptor Cannabinoid CB1Pregnancyactive avoidance behaviourWIN 55212-2Cells CulturedCerebral CortexBehavior AnimalGlutamate receptorBraincortical cell culturesCalcium Channel Blockersactive avoidance behaviour; basal and k plus -evoked glutamate levels; basal and k+-evoked glutamate levels; cortical cell cultures; homing behaviour; maternal marijuana consumption; ultrasonic vocalizationPrenatal Exposure Delayed EffectsChloratesNMDA receptorbasal and K+-evoked glutamate levelsFemaleMicrotubule-Associated Proteinsmedicine.drugAgonistmedicine.medical_specialtyOffspringmedicine.drug_classCognitive NeuroscienceMorpholinesGlutamic Acidmaternal marijuana consumptionNeurotransmissionBiologyNaphthalenesReceptors N-Methyl-D-AspartateCellular and Molecular NeuroscienceGlutamatergicInternal medicinemedicineAvoidance LearningAnimalsRats WistarBenzoxazinesRatsultrasonic vocalizationEndocrinologyAnimals Newbornhoming behaviourVocalization AnimalExtracellular SpaceNeurosciencedescription
The aim of this study was to investigate whether prenatal exposure to the cannabinoid CB1 receptor agonist WIN 55,212-2 (WIN) at a daily dose devoid of overt signs of toxicity and/or gross malformations (0.5 mg/kg, gestation days 5-20), influences cortical glutamatergic neurotransmission, learning and emotional reactivity in rat offspring. Basal and K+-evoked extracellular glutamate levels were significantly lower in cortical cell cultures obtained from pups exposed to WIN during gestation with respect to those measured in cultures obtained from neonates born from vehicle-treated dams. The addition of NMDA to cortical cell cultures from neonates born from vehicle-treated dams concentration-dependently increased glutamate levels, and this was absent in cell cultures obtained from WIN-exposed pups. WIN-exposed rats also revealed a poorer performance in homing (10-12 days of age) and active avoidance tests (80 days of age) as well as a decrease in the rate of separation-induced ultrasonic emission (10 days of age). Finally, prenatal exposure to WIN induced a reduction in the number of cortical neuronal population. These findings (i) provide evidence for a deficit in cortical glutamatergic neurotransmission and behaviour in the rat neonate following prenatal exposure to WIN; and (ii) suggest that the reduction in cortical glutamatergic neurotransmission, NMDA receptor activity and alterations in neuronal development might underlie, at least in part, the learning deficit and decreased emotional reactivity observed in the offspring.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2005-01-01 |