Chronic THC during adolescence increases the vulnerability to stress-induced relapse to heroin seeking in adult rats.
Serena Stopponi, Laura Soverchia, Massimo Ubaldi, Andrea Cippitelli, Giovanni Serpelloni, Roberto Ciccocioppo
European Neuropsychopharmacology July 2014 DOI: 10.1016/j.euroneuro.2013.12.012 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Adolescent rats (postnatal day 35-46 at treatment), tested into adulthood |
| Interventions | delta-9-tetrahydrocannabinol (THC) heroin yohimbine |
| Dose | THC 2.5-10 mg/kg daily; heroin 20 μg per infusion; yohimbine 1.25 mg/kg |
| Duration | THC treatment from postnatal day 35 to 46; anxiety testing one week after; heroin self-administration training starting postnatal day 75; extinction and reinstatement thereafter |
| Measures | elevated plus maze (EPM), heroin self-administration (acquisition and intake), extinction, yohimbine-induced reinstatement of lever pressing |
| Topics | Addiction Anxiety Cannabis |
| Keywords | Adolescence Self-administration |
| Key findings | Rats chronically treated with THC during adolescence showed higher anxiety-like behavior than controls and, after extinction of heroin self-administration, yohimbine elicited significantly greater heroin seeking. Acquisition of heroin self-administration and baseline heroin intake did not differ between groups. The authors conclude that adolescent THC exposure heightens anxiety and increases vulnerability to drug relapse in adulthood. |
Abstract
Cannabis derivatives are among the most widely used illicit substances among young people. The addictive potential of delta-9-tetrahydrocannabinol (THC), the major active ingredient of cannabis is well documented in scientific literature. However, the consequence of THC exposure during adolescence on occurrence of addiction for other drugs of abuse later in life is still controversial. To explore this aspect of THC pharmacology, in the present study, we treated adolescent rats from postnatal day (PND) 35 to PND-46 with increasing daily doses of THC (2.5-10mg/kg). One week after intoxication, the rats were tested for anxiety-like behavior in the elevated plus maze (EPM) test. One month later (starting from PND 75), rats were trained to operantly self-administer heroin intravenously. Finally, following extinction phase, reinstatement of lever pressing elicited by the pharmacological stressor, yohimbine (1.25mg/kg) was evaluated. Data revealed that in comparison to controls, animals treated with chronic THC during adolescence showed a higher level of anxiety-like behavior. When tested for heroin (20μg per infusion) self-administration, no significant differences were observed in both the acquisition of operant responding and heroin intake at baseline. Noteworthy, following the extinction phase, administration of yohimbine elicited a significantly higher level of heroin seeking in rats previously exposed to THC. Altogether these findings demonstrate that chronic exposure to THC during adolescence is responsible for heightened anxiety and increased vulnerability to drug relapse in adulthood.
Comparable studies
Other preclinical and animal studies on cannabis for anxiety, most cited first.
Citations in the library
Cited by 14
- Adolescent cannabinoid exposure induces irritability-like behavior and cocaine cross-sensitization without affecting the escalation of cocaine self-administration in adulthood Scientific Reports September 11, 2018
- Lasting effects of repeated Δ9-tetrahydrocannabinol (THC) vapor inhalation during adolescence in male and female rats bioRxiv (Cold Spring Harbor Laboratory) September 25, 2018
- Long-term effects of adolescent THC exposure on anxiety-like behavior and cognitive function in male rats Psychopharmacology April 23, 2026
- Divergent outcomes of delta 9 - tetrahydrocannabinol (THC) in adolescence on mesocortical dopamine and cognitive development in male and female mice. Psychopharmacology October 2025
- THC and CBD: Villain versus Hero? Insights into Adolescent Exposure. International Journal of Molecular Sciences March 9, 2023
and 9 more in the library
Cites 12
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- Pretreatment with Δ9-tetrahydrocannabinol (THC) increases cocaine-stimulated activity in adolescent but not adult male rats. Pharmacology, Biochemistry, and Behavior January 2012
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- Cannabis and psychosis/schizophrenia: human studies European Archives of Psychiatry and Clinical Neuroscience July 16, 2009
- Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. European Neuropsychopharmacology November 2008
and 7 more in the library