Chronic delta 9-tetrahydrocannabinol during adolescence provokes sex-dependent changes in the emotional profile in adult rats: behavioral and biochemical correlates.
Tiziana Rubino, Daniela Vigano', Natalia Realini, Cinzia Guidali, Daniela Braida, Valeria Capurro, Chiara Castiglioni, Francesca Cherubino, Patrizia Romualdi, Sanzio Candeletti, Mariaelvina Sala, Daniela Parolaro
Neuropsychopharmacology October 2008 DOI: 10.1038/sj.npp.1301664 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Adolescent female and male rats |
| Intervention | Delta(9)-tetrahydrocannabinol (THC) |
| Dose | increasing doses for 11 days |
| Duration | 11-day treatment (PND 35-45), assessments at adulthood (PND 75) |
| Measures | elevated plus maze, open-field test, forced swim test, sucrose preference |
| Topics | Cannabis |
| Key findings | THC exposure during adolescence reduced CB1 receptor levels and coupling in brain regions of adult rats, with sex-specific patterns. Female rats exhibited depressive-like behavior and anhedonia, while male rats showed anhedonia but not behavioral despair, suggesting sex-dependent long-term effects of adolescent cannabis use. |
Abstract
Few and often contradictory reports exist on the long-term neurobiological consequences of cannabinoid consumption in adolescents. The endocannabinoid system plays an important role during the different stages of brain development as cannabinoids influence the release and action of different neurotransmitters and promote neurogenesis. This study tested whether long-lasting interference by cannabinoids with the developing endogenous cannabinoid system during adolescence caused persistent behavioral alterations in adult rats. Adolescent female and male rats were treated with increasing doses of Delta(9)-tetrahydrocannabinol (THC) for 11 days (postnatal day (PND) 35-45) and left undisturbed until adulthood (PND 75) when behavioral and biochemical assays were carried out. CB1 receptor level and CB1/G-protein coupling were significantly reduced by THC exposure in the amygdala (Amyg), ventral tegmental area (VTA) and nucleus accumbens (NAc) of female rats, whereas male rats had significant alterations only in the amygdala and hippocampal formation. Neither female nor male rats showed any changes in anxiety responses (elevated plus maze and open-field tests) but female rats presented significant 'behavioral despair' (forced swim test) paralleled by anhedonia (sucrose preference). In contrast, male rats showed no behavioral despair but did present anhedonia. This different behavioral picture was supported by biochemical parameters of depression, namely CREB alteration. Only female rats had low CREB activity in the hippocampal formation and prefrontal cortex and high activity in the NAc paralleled by increases in dynorphin expression. These results suggest that heavy cannabis consumption in adolescence may induce subtle alterations in the emotional circuit in female rats, ending in depressive-like behavior, whereas male rats show altered sensitivity to rewarding stimuli.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 68
- Cannabis Use during Adolescent Development: Susceptibility to Psychiatric Illness Frontiers in Psychiatry 2013
- Long-term consequences of adolescent cannabinoid exposure in adult psychopathology Frontiers in Neuroscience November 10, 2014
- Drug models of schizophrenia. Therapeutic Advances in Psychopharmacology February 1, 2015
- 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
- Sex-Dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption PLoS One November 4, 2013
and 63 more in the library
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