Neurotoxicity Research

, Volume 15, Issue 4, pp 291–302 | Cite as

The Depressive Phenotype Induced in Adult Female Rats by Adolescent Exposure to THC is Associated with Cognitive Impairment and Altered Neuroplasticity in the Prefrontal Cortex

  • T. Rubino
  • N. Realini
  • D. Braida
  • T. Alberio
  • V. Capurro
  • D. Viganò
  • C. Guidali
  • M. Sala
  • M. Fasano
  • D. Parolaro


We recently demonstrated that Δ9-tetrahydrocannabinol (THC) chronic administration in female adolescent rats induces alterations in the emotional circuit ending in depressive-like behavior in adulthood. Since cognitive dysfunction is a major component of depression, we assessed in these animals at adulthood different forms of memory. Adolescent female rats were treated with THC or its vehicle from 35 to 45 post-natal days (PND) and left undisturbed until their adulthood (75 PND) when aversive and spatial memory was assessed using the passive avoidance and radial maze tasks. No alteration was found in aversive memory, but in the radial maze THC pre-treated animals exhibited a worse performance than vehicles, suggesting a deficit in spatial working memory. To correlate memory impairment to altered neuroplasticity, level of marker proteins was investigated in the hippocampus and prefrontal cortex, the most relevant areas for learning and memory. A significant decrease in synaptophysin and PSD95 proteins was found in the prefrontal cortex of THC pre-treated rats, with no alterations in the hippocampus. Finally, proteomic analysis of the synapses in the prefrontal cortex revealed the presence of less active synapses characterized by reduced ability in maintaining normal synaptic efficiency. This picture demonstrates the presence of cognitive impairment in THC-induced depressive phenotype.


Adolescent female rats Cannabinoids Neuroproteomics Spatial working memory Synaptic markers 



This work was supported by grants from the Italian Governmental Department of Drugs of Abuse and University of Insubria (FAR2007, FAR2008). We wish to thank Michela Matteoli (University of Milan) for her helpful suggestions on neuroplasticity markers.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • T. Rubino
    • 1
  • N. Realini
    • 1
  • D. Braida
    • 2
  • T. Alberio
    • 1
  • V. Capurro
    • 2
  • D. Viganò
    • 1
  • C. Guidali
    • 1
  • M. Sala
    • 2
  • M. Fasano
    • 1
  • D. Parolaro
    • 1
  1. 1.DBSF and Neuroscience CenterUniversity of InsubriaBusto ArsizioItaly
  2. 2.Department of Pharmacology, Chemotherapy and Medical ToxicologyUniversity of MilanMilanItaly

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