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Behavioral Responses to Acute and Sub-chronic Administration of the Synthetic Cannabinoid JWH-018 in Adult Mice Prenatally Exposed to Corticosterone

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Abstract

Recent data indicate that both availability and consumption of synthetic and natural psychoactive substances, marketed under the name of “legal highs”, has increased. Among them, the aminoalkylindole-derivative JWH-018 is widely distributed due to its capability of binding the cannabinoid receptors CB1 and CB2 thereby mimicking the effects of classical drug agonists. To address whether the behavioral effects of the synthetic compound JWH-018 are similar to those induced by classical cannabinoid agonists, we investigated, in outbred CD1 mice, the consequences of its acute and sub-chronic administration (0, 0.03, 0.1, or 0.3 mg/kg, IP) at the level of body temperature, pain perception, general locomotion, and anxiety. In order to address whether the exposure to precocious stressors-modified individual reactivity to this psychoactive substance, we also investigated its effects in adult mice previously exposed to prenatal stress in the form of corticosterone supplementation in the maternal drinking water (33 or 100 mg/L). In the absence of major effects on motor coordination, JWH-018-reduced body temperature, locomotion and pain reactivity, and increased indices of anxiety. Prenatal corticosterone administration-reduced individual sensitivity to the effects of JWH-018 administration in all the aforementioned parameters. This altered response is not due to variations in JWH-018 metabolism. Present data support the hypothesis that precocious stress may affect, in the long-term, the functional status, and reactivity of the endocannabinoid system.

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Acknowledgments

This study was supported by the grant ‘‘ECS-EMOTION: Resilience’’ to G.L. and S.M. and by the Grant “National Early Warning System” to T.M. from the Department for Antidrug Policies c/o Presidency of the Council of Ministers, Italy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Section of Behavioural Neuroscience, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy

    Simone Macrì, Lara Lanuzza, Chiara Ceci & Giovanni Laviola

  2. Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy

    Gustavo Merola, Stefano Gentili & Teodora Macchia

  3. Laboratory of Analytical Toxicology, IRCCS Foundation Policlinico San Matteo, Pavia, Italy

    Antonella Valli

  4. Section of Behavioural Neuroscience, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, block 19, floor D, room 15, 00161, Rome, Italy

    Giovanni Laviola

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  1. Simone Macrì
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  2. Lara Lanuzza
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  3. Gustavo Merola
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Correspondence to Giovanni Laviola.

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Simone Macrì and Lara Lanuzza equally contributed to the study.

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Macrì, S., Lanuzza, L., Merola, G. et al. Behavioral Responses to Acute and Sub-chronic Administration of the Synthetic Cannabinoid JWH-018 in Adult Mice Prenatally Exposed to Corticosterone. Neurotox Res 24, 15–28 (2013). https://doi.org/10.1007/s12640-012-9371-2

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