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Risk for Psychiatric Diseases Following Cannabis Abuse in Adolescence: An Experimental Study

This study explores the long-term effects of adolescent THC exposure on the development of psychiatric diseases in adulthood. Findings suggest that chronic cannabis abuse during adolescence can lead to altered brain functionality and behavior in adulthood, highlighting the vulnerability of the adolescent brain to the persistent effects of cannabinoids. The study also examines sex-dependent effects and potential underlying mechanisms.

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Risk for Psychiatric Diseases Following Cannabis Abuse in Adolescence: An Experimental Study

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  1. Risk for psychiatric diseases following cannabis abuse in adolescence :an experimental studyDaniela ParolaroUniv of Insubria

  2. Beginning of behavioral tests Beginning of treatment Arrival of animals End of treatment Postnatal day (PND) 75 28 35 36 37 38 39 40 41 42 43 44 45 2.5 mg/kg THC Twice a day 10 mg/kg THC Twice a day 5 mg/kg THC Twice a day DRUG-FREE Characterization of the phenotype present in adult rats pre-exposed to THC in adolescence

  3. ♂ Adolescent THC exposureinduced… No alteration in anxiety behaviour No presence of behavioural despair Spatial working memory impairments in the radial maze reduced markers of neuronal plasticity in the hippocampus changes in dendritic morphology and spine density in dentate granule cells of the hippocampus Rubino et al., Neuropsychopharmacol 2008; Hippocampus 2009

  4. Adult THC exposure did not induce ♂ cognitive impairment in the radial maze alteration in markers of neural plasticity in the hippocampus

  5. COGNITION Classic Spatial ♀ Novel Object Recognition Test

  6. EMOTIONALITY ♀ Social Interaction Test Habituation phase (10 min) Test phase (10 min)

  7. EMOTIONALITY ForcedSwim Test ♀ • Single session • 15 minutes • Immobility • Climbing • Swimming

  8. Anhedonia through Fonzies intake Anhedonia through sucrose preference ♀ Anhedonia a b

  9. PCP 2.5 mg/kg Locomotor activity Stereotypies ONLY THC-TREATED RATS SHOW HYPERLOCOMOTION AND INCREASED STEREOTYPED BEHAVIORS IN RESPONSE TO A LOW DOSE OF PCP COMPARED TO CONTROL ANIMALS

  10. Adolescent THC exposure in female rats induces cognitive deficit, social withdrawal, avolition, anhedonia and sensitizes to PCP The hypersensitivity to PCP seems to be due to increased neuronal activation in the caudate putamen and nucleus accumbensas confirmed by enhanced glutamate release in the dorsal striatum Schizoaffective-likephenotype

  11. Adult female rats exposed to THC did not show altered phenotype a b c d e Realini et al 2010

  12. ♀ Adolescent THC exposure led to decreased GAD 67 levels in adulthood paralleled by decreased basal GABA release in the prefrontal cortex GAD67 LEVELS BASAL GABA RELEASE

  13. THC GluN2B- containing GluA1- containing GluN2A- containing GluA2- containing Protein levels GluN2A- containing GluA2- containing GluN2B- containing GluA1- containing DEVELOPMENT ADOLESCENT THC EXPOSURE ALTERS THE REARRANGEMENT OF NMDA AND AMPA RECEPTOR SUBUNITS, RESULTING IN THE PRESENCE OF IMMATURE, MORE EXCITABLE, GLUTAMATERGIC SYNAPSES IN THE ADULT PFC

  14. ♀ Adolescent THC exposure decreased spine density at the distal portion of basilar dendrites

  15. why adolescence?

  16. the brain continues to develop throughout adolescence important structural and functional changes in synaptic plasticity and neural connectivity At cellular level, changes in gray matter volumes appear to be associated with pruning in later adolescence

  17. Endocannabinoidsas retrograde messengers

  18. THC ECS Adolescent brain lasting changes in brain and behavior?

  19. CONCLUSIONS The endocannabinoid system undergoes maturational events during adolescence that are impaired by chronic THC exposure correct neuronal refinement peculiar of the adolescent brain altered brain functionality and behavior at adulthood

  20. The possible problems associated with marijuana consumption in adolescence suggest that the adolescence developmental phase represents a vulnerable time period for persistent effects on synaptic plasticity that could underline adverse actions of cannabinoids in adulthood.These effects are sex-dependent. Daniela.parolaro@uninsubria.it

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