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.
Tiziana Rubino, Natalia Realini, Daniela Braida, T Alberio, Valeria Capurro, Daniela Viganò, Cinzia Guidali, M Sala, Mauro Fasano, Daniela Parolaro
Neurotoxicity Research May 2009 DOI: 10.1007/s12640-009-9031-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Female adolescent rats treated from postnatal day 35 to 45 and assessed in adulthood at postnatal day 75 |
| Intervention | Delta(9)-tetrahydrocannabinol (THC) |
| Duration | Treated from 35 to 45 postnatal days, assessed at 75 postnatal days |
| Measures | passive avoidance task, radial maze task |
| Topics | Cannabis Neuroplasticity |
| Key findings | Adult female rats treated with THC during adolescence performed worse than vehicle-treated rats on a radial maze spatial working memory task, with no difference in aversive memory. THC-treated rats also showed decreased synaptophysin and PSD95 in the prefrontal cortex, but not hippocampus, and proteomic analysis indicated less active synapses with reduced synaptic efficiency. |
Abstract
We recently demonstrated that Delta(9)-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.
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Citations in the library
Cited by 27
- Long-term consequences of adolescent cannabinoid exposure in adult psychopathology Frontiers in Neuroscience November 10, 2014
- Susceptibility of the adolescent brain to cannabinoids: long-term hippocampal effects and relevance to schizophrenia Translational Psychiatry November 27, 2012
- Sex‐dependent long‐term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats British Journal of Pharmacology November 15, 2013
- A Proteomic View of Cellular and Molecular Effects of Cannabis Biomolecules September 27, 2021
- Prolonged incubation with Δ9-tetrahydrocannabinol but not with cannabidiol induces synaptic alterations and mitochondrial impairment in immature and mature rat organotypic hippocampal slices. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie February 1, 2025
and 22 more in the library
Cites 3
- Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus August 2009
- Chronic delta 9-tetrahydrocannabinol during adolescence provokes sex-dependent changes in the emotional profile in adult rats: behavioral and biochemical correlates. Neuropsychopharmacology October 2008
- Sex differences in the effects of delta9-tetrahydrocannabinol on spatial learning in adolescent and adult rats. Behavioural Pharmacology September 2007