Δ 9-Tetrahydrocannabinol During Adolescence Reprograms the Nucleus Accumbens Transcriptome, Affecting Reward Processing, Impulsivity, and Specific Aspects of Cocaine Addiction-Like Behavior in a Sex-Dependent Manner.
Javier Orihuel, Roberto Capellán, David Roura-Martínez, Marcos Ucha, Emilio Ambrosio, Alejandro Higuera-Matas
The International Journal of Neuropsychopharmacology November 12, 2021 DOI: 10.1093/ijnp/pyab058 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Male and female adolescent rats exposed to THC, studied in adulthood |
| Intervention | Δ9-tetrahydrocannabinol (THC) |
| Measures | Pavlovian conditioned approach, Pavlovian to instrumental transfer, habit formation, waiting impulsivity, 2-CSRTT task, RNASeq, cocaine self-administration, progressive ratio schedule |
| Topics | Cannabis Addiction |
| Keywords | Rnaseq Cocaine Reward |
| Key findings | Adolescent THC exposure altered specific reward- and cocaine-related behaviors and nucleus accumbens gene expression in adulthood in a sex-specific manner. THC increased goal-tracking in both sexes and enhanced Pavlovian-to-instrumental transfer especially in males, without affecting habit formation. THC-exposed males self-administered more cocaine under a progressive ratio schedule, and females showed a higher rebound upon resuming continuous access and reduced drug-seeking after 30 days of withdrawal. |
Abstract
Cannabis exposure during adolescence is associated with emotional and motivational alterations that may entail an enhanced risk of developing psychiatric disorders. In rodent models, exposure to cannabinoids during adolescence leads to increased self-administration of opiates and cocaine, however, the psychological and neural mechanisms and the sex-specificity of this phenomenon are largely unknown. We exposed male and female adolescent rats to Δ9-tetrahydrocannabinol (THC) and studied at adulthood the effects of such treatment on psychological processes related to reward, such as Pavlovian conditioned approach, Pavlovian to instrumental transfer, habit formation and waiting impulsivity. In the light of these data and given the involvement of the nucleus accumbens in the processes examined, we performed an RNASeq transcriptomic study and assessed cocaine addiction-like behavior. THC exposure increased goal-tracking (in males and females) and enhanced Pavlovian to instrumental transfer (especially in males) but did not affect habit formation. THC-exposed rats exhibited subtle, state-dependent changes in premature responding in the 2-CSRTT task. RNASeq data showed gene expression alterations in a marked sex-specific manner. While no effects were found on the acquisition of cocaine self-administration or punished drug-seeking, rats exposed to THC self-administered more cocaine under a progressive ratio schedule (males), had a higher rebound upon returning to continuous access to the drug (females) and showed reduced drug-seeking after 30 days of withdrawal (females). Adolescent THC affects specific aspects of reward- (and cocaine-) guided behavior and the function of a key brain region mediating these effects, in a remarkable sex-specific manner.
Comparable studies
Other preclinical and animal studies on cannabis for addiction, most cited first.
Citations in the library
Cited by 4
- Adolescent cannabinoid vapour exposure sex-dependently alters the relationship between vulnerability traits and ethanol self-administration and modifies naltrexone actions on ethanol intake in rats. Neuropharmacology May 1, 2026
- Adolescent female rats are resistant to the affective and cognitive impacts of Δ9-tetrahydrocannabinol exposure despite long-lasting molecular and neuronal disturbances in the hippocampal-hypothalamic network. Psychopharmacology November 1, 2025
- Chronic Δ9-tetrahydrocannabinol exposure in adolescent nonhuman primates: persistent abnormalities in economic demand and brain functional connectivity. Neuropsychopharmacology February 1, 2025
- Long-term effects of THC exposure on reward learning and motivated behavior in adolescent and adult male rats. Psychopharmacology May 2023
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