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Chronic THC during adolescence increases the vulnerability to stress-induced relapse to heroin seeking in adult rats.
Eur Neuropsychopharmacol. 2014 Jul; 24(7):1037-45.EN

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+Show Affiliations

School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy.School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy.School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy.School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy.Dipartimento Politiche Antidroga, Presidenza del Consiglio dei Ministri, Italy.School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy. Electronic address: roberto.ciccocioppo@unicam.it.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24412506

Citation

Stopponi, Serena, et al. "Chronic THC During Adolescence Increases the Vulnerability to Stress-induced Relapse to Heroin Seeking in Adult Rats." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 24, no. 7, 2014, pp. 1037-45.
Stopponi S, Soverchia L, Ubaldi M, et al. Chronic THC during adolescence increases the vulnerability to stress-induced relapse to heroin seeking in adult rats. Eur Neuropsychopharmacol. 2014;24(7):1037-45.
Stopponi, S., Soverchia, L., Ubaldi, M., Cippitelli, A., Serpelloni, G., & Ciccocioppo, R. (2014). Chronic THC during adolescence increases the vulnerability to stress-induced relapse to heroin seeking in adult rats. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 24(7), 1037-45. https://doi.org/10.1016/j.euroneuro.2013.12.012
Stopponi S, et al. Chronic THC During Adolescence Increases the Vulnerability to Stress-induced Relapse to Heroin Seeking in Adult Rats. Eur Neuropsychopharmacol. 2014;24(7):1037-45. PubMed PMID: 24412506.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic THC during adolescence increases the vulnerability to stress-induced relapse to heroin seeking in adult rats. AU - Stopponi,Serena, AU - Soverchia,Laura, AU - Ubaldi,Massimo, AU - Cippitelli,Andrea, AU - Serpelloni,Giovanni, AU - Ciccocioppo,Roberto, Y1 - 2013/12/24/ PY - 2013/05/10/received PY - 2013/12/13/revised PY - 2013/12/16/accepted PY - 2014/1/14/entrez PY - 2014/1/15/pubmed PY - 2015/2/13/medline KW - Addiction KW - Adolescence KW - Anxiety KW - Rat KW - Self-administration KW - THC SP - 1037 EP - 45 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 24 IS - 7 N2 - 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. SN - 1873-7862 UR - https://www.unboundmedicine.com/medline/citation/24412506/Chronic_THC_during_adolescence_increases_the_vulnerability_to_stress_induced_relapse_to_heroin_seeking_in_adult_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-977X(13)00357-X DB - PRIME DP - Unbound Medicine ER -