title: Chronic THC during adolescence increases the vulnerability to stress-induced relapse to heroin seeking in adult rats.
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.
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Stopponi
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Soverchia
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Ubaldi
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cippitelli
authors.affiliation: Dipartimento Politiche Antidroga, Presidenza del Consiglio dei Ministri, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Serpelloni
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy. Electronic address: roberto.ciccocioppo@unicam.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccocioppo
mesh_terms: D000818:Animals; D016739:Behavior, Addictive; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D013759:Dronabinol / Q000494:pharmacology*; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D003932:Heroin / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013312:Stress, Physiological / Q000187:drug effects*; D013315:Stress, Psychological
chemical_list: D003932:Heroin; D013759:Dronabinol
keywords: Addiction; Adolescence; Anxiety; Rat; Self-administration; THC