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Hallucinatory and rewarding effect of salvinorin A in zebrafish: κ-opioid and CB1-cannabinoid receptor involvement

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Abstract

Rationale

The hallucinatory effect and potential abuse of salvinorin A, the major ingredient of Salvia divinorum, has not been documented in animals.

Objective

The effects of salvinorin A on the zebrafish (Danio rerio) model, through its swimming behavior and conditioned place preference (CPP) task, was studied.

Materials and methods

Swimming activity was determined in a squared observational chamber after an i.m. treatment of salvinorin A (0.1–10 μg/kg). For the CPP test, zebrafish were given salvinorin A (0.2 and 1 μg/kg) or vehicle and evaluated in a two-compartment chamber.

Results

Salvinorin A (0.1 and 0.2 μg/kg) induced accelerated swimming behavior in comparison with vehicle, whereas a “trance-like” effect, at doses as 5 and 10 μg/kg, was obtained. Pretreatment with the κ-opioid antagonist, nor-binaltorphimine (nor-BNI; 10 mg/kg) and the cannabinoid type 1 (CB1) antagonist, rimonabant (1 mg/kg), blocked salvinorin A-induced both stimulating and depressive effects obtained at a dose of 0.2 and 10 μg/kg, respectively. In the CPP test, salvinorin A (0.2 and 0.5 μg/kg) produced an increase in the time spent in the drug-associated compartment. A dose of 1 μg/kg produced no effect, whereas a dose of 80 μg/kg induced aversion. Pretreatment with nor-BNI or rimonabant fully reversed the reinforcing properties of salvinorin A (0.5 μg/kg).

Conclusions

Taken together, these results indicate that salvinorin A, as is sometimes reported in humans, exhibits rewarding effects, independently from its motor activity, suggesting the usefulness of the zebrafish model to study addictive behavior. These effects appear mediated by activation of both κ-opioid and cannabinoid CB1 receptors.

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Acknowledgement

The authors are grateful for the financial support from regione Lombardia-Direzione Famiglia e Solidarietà sociale (MDMA).

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Authors and Affiliations

  1. Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Via Vanvitelli 32, 20129, Milan, Italy

    Daniela Braida, Valeria Limonta, Simona Pegorini, Alessia Zani & Mariaelvina Sala

  2. Behavioural Pharmacology and Drug Dependence Center, University of Milan, Via Vanvitelli 32, 20129, Milan, Italy

    Chiara Guerini-Rocco & Enzo Gori

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  1. Daniela Braida
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  2. Valeria Limonta
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  3. Simona Pegorini
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  4. Alessia Zani
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  7. Mariaelvina Sala
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Correspondence to Daniela Braida.

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Braida, D., Limonta, V., Pegorini, S. et al. Hallucinatory and rewarding effect of salvinorin A in zebrafish: κ-opioid and CB1-cannabinoid receptor involvement. Psychopharmacology 190, 441–448 (2007). https://doi.org/10.1007/s00213-006-0639-1

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  • DOI: https://doi.org/10.1007/s00213-006-0639-1

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