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Eur Neuropsychopharmacol. 2019 Feb 14. pii: S0924-977X(19)30158-0. doi: 10.1016/j.euroneuro.2019.02.001. [Epub ahead of print]

Increased sensitivity to Δ9-THC-induced rewarding effects after seven-week exposure to electronic and tobacco cigarettes in mice.

Author information

1
CNR, Institute of Neuroscience, Milan, Italy.
2
CNR, Institute of Neuroscience, Milan, Italy; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy.
3
Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy.
4
Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and Neurotechnology, Università degli Studi di Modena e Reggio Emilia, Modena, Italy.
5
CNR, Institute of Neuroscience, Milan, Italy; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy. Electronic address: c.gotti@in.cnr.it.

Abstract

Cigarette (CIG) smoking often precedes the use of illegal drugs. Electronic-cigarettes (e-CIGs) have been promoted as a means of stopping smoking and reducing the harmful effects of CIGs on the population. However, although e-CIGs eliminate some of the morbidity associated with combustible tobacco, they are still nicotine-delivery devices. In order to study whether the nicotine delivered via e-CIG acts as "a gateway drug" to the use of cannabis, we analysed the behavioural and molecular effects of 7 weeks' pre-exposure to air (AIR), e-CIGs or CIGs on addiction-related conditioned place preference (CPP) in mice using a sub-threshold (0.01 mg/kg) dose of delta-9-tetrahydrocannabinol (Δ9-THC), the principal psychoactive constituent of cannabis. After 8 and 66 days of withdrawal, this Δ9-THC dose was ineffective in inducing CPP in mice pre-exposed to pump-driven AIR, but very effective in mice pre-exposed to e-CIGs or CIGs. Exposure to e-CIGs or CIGs increases the expression of ΔFosB in the nucleus accumbens (NAc), which remains high during short-term e-CIG or CIG withdrawal and long-term CIG withdrawal and is not influenced by treatment with Δ9-THC. At the end of e-CIG or CIG exposure and during withdrawal, the mice also had a higher AMPA receptors GluA1/GluA2-3 ratio in the NAc. Chronic nicotine exposure increases sensitivity to rewarding effects of Δ9-THC in mice and produces long-lasting neurobiological changes regardless of the delivery method (CIG vs. e-CIG). The exposure to passive tobacco smoke or e-CIG vapours can similarly increase vulnerability to the effects of cannabis and possibly other drugs of abuse.

KEYWORDS:

AMPA receptors; CB1 receptors; Cigarette smoke; Conditioned place preference; Electronic cigarette vapour; Δ(9)-THC

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