Alterations of prefrontal cortex GABAergic transmission in the complex psychotic-like phenotype induced by adolescent delta-9-tetrahydrocannabinol exposure in rats.
Erica Zamberletti, Sarah Beggiato, Luca Steardo, Pamela Prini, Tiziana Antonelli, Luca Ferraro, Tiziana Rubino, Daniela Parolaro
Neurobiology of Disease March 1, 2014 DOI: 10.1016/j.nbd.2013.10.028 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Female Sprague-Dawley rats |
| Intervention | delta-9-tetrahydrocannabinol (THC) |
| Duration | Adolescence (PND 35-45) treatment, tested in adulthood (PND 75) |
| Topics | Cannabis |
| Keywords | Adolescent THC Treatment Behavior Gaba Gad67 Glutamate Prefrontal cortex |
| Key points | Adolescent THC exposure in female rats leads to long-term behavioral alterations and reduced GAD67 and GABA levels in the prefrontal cortex, supporting a link to psychotic-like behavior in adulthood. |
Abstract
Although several findings indicate an association between adolescent cannabis abuse and the risk to develop schizophrenia later in life, the evidence for a causal relationship is still inconclusive. In the present study, we investigated the emergence of psychotic-like behavior in adult female rats chronically exposed to delta-9-tetrahydrocannabinol (THC) during adolescence. To this aim, female Sprague-Dawley rats were treated with THC during adolescence (PND 35-45) and, in adulthood (PND 75), a series of behavioral tests and biochemical assays were performed in order to investigate the long-term effects of adolescent THC exposure. Adolescent THC pretreatment leads to long-term behavioral alterations, characterized by recognition memory deficits, social withdrawal, altered emotional reactivity and sensitization to the locomotor activating effects of acute PCP. Moreover, since cortical disinhibition seems to be a key feature of many different animal models of schizophrenia and GABAergic hypofunction in the prefrontal cortex (PFC) has been observed in postmortem brains from schizophrenic patients, we then investigated the long-lasting consequences of adolescent THC exposure on GABAergic transmission in the adult rat PFC. Biochemical analyses revealed that adolescent THC exposure results in reduced GAD67 and basal GABA levels within the adult PFC. GAD67 expression is reduced both in parvalbumin (PV)- and cholecystokinin (CCK)-containing interneurons; this alteration may be related to the altered emotional reactivity triggered by adolescent THC, as silencing PFC GAD67 expression through a siRNA-mediated approach is sufficient to impact rats' behavior in the forced swim test. Finally, the cellular underpinnings of the observed sensitized response to acute PCP in adult THC-treated rats could be ascribed to the increased cFos immunoreactivity and glutamate levels in the PFC and dorsal striatum. The present findings support the hypothesis that adolescent THC exposure may represent a risk factor for the development of a complex psychotic-like behavior in adulthood.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 33
- Long-term consequences of adolescent cannabinoid exposure in adult psychopathology Frontiers in Neuroscience November 10, 2014
- The Relationship Between Cannabis, Cognition, and Schizophrenia: It’s Complicated Current Topics in Behavioral Neurosciences 2022
- Effects of Cannabinoid Exposure during Neurodevelopment on Future Effects of Drugs of Abuse: A Preclinical Perspective International Journal of Molecular Sciences September 15, 2021
- The antioxidant N-acetylcysteine prevents cortical neuropathological phenotypes caused by adolescent Δ-9-tetrahydrocannabinol exposure in male rats. Translational Psychiatry October 6, 2025
- Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats. Psychopharmacology February 1, 2025
and 28 more in the library
Cites 14
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- High-potency cannabis and the risk of psychosis The British Journal of Psychiatry November 30, 2009
- Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study BMJ March 1, 2011
- Dysfunctional prefrontal cortical network activity and interactions following cannabinoid receptor activation. Journal of Neuroscience October 26, 2011
- Chronic URB597 treatment at adulthood reverted most depressive-like symptoms induced by adolescent exposure to THC in female rats. Neuropharmacology 2011
and 9 more in the library