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

Daniela Braida, Valeria Limonta, Simona Pegorini, Alessia Zani, Chiara Guerini-Rocco, Enzo Gori, Mariaelvina Sala

Research output: Contribution to journalArticle

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 (CB 1) 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 CB 1 receptors.

Original languageEnglish
Pages (from-to)441-448
Number of pages8
JournalPsychopharmacology
Volume190
Issue number4
DOIs
Publication statusPublished - Mar 2007

Fingerprint

salvinorin A
Cannabinoid Receptor CB1
Zebrafish
Opioid Analgesics
rimonabant
Cannabinoid Receptor Antagonists
Salvia
Addictive Behavior
Cannabinoid Receptors
Narcotic Antagonists
Cannabinoids

Keywords

  • Conditioned place preference
  • Nor-binalthorphimine
  • Salvia divinorum
  • SR 141716A
  • Swimming behavior
  • Zebrafish

ASJC Scopus subject areas

  • Pharmacology

Cite this

Braida, D., Limonta, V., Pegorini, S., Zani, A., Guerini-Rocco, C., Gori, E., & Sala, M. (2007). Hallucinatory and rewarding effect of salvinorin A in zebrafish: κ-opioid and CB1-cannabinoid receptor involvement. Psychopharmacology, 190(4), 441-448. https://doi.org/10.1007/s00213-006-0639-1

Hallucinatory and rewarding effect of salvinorin A in zebrafish : κ-opioid and CB1-cannabinoid receptor involvement. / Braida, Daniela; Limonta, Valeria; Pegorini, Simona; Zani, Alessia; Guerini-Rocco, Chiara; Gori, Enzo; Sala, Mariaelvina.

In: Psychopharmacology, Vol. 190, No. 4, 03.2007, p. 441-448.

Research output: Contribution to journalArticle

Braida, D, Limonta, V, Pegorini, S, Zani, A, Guerini-Rocco, C, Gori, E & Sala, M 2007, 'Hallucinatory and rewarding effect of salvinorin A in zebrafish: κ-opioid and CB1-cannabinoid receptor involvement', Psychopharmacology, vol. 190, no. 4, pp. 441-448. https://doi.org/10.1007/s00213-006-0639-1
Braida, Daniela ; Limonta, Valeria ; Pegorini, Simona ; Zani, Alessia ; Guerini-Rocco, Chiara ; Gori, Enzo ; Sala, Mariaelvina. / Hallucinatory and rewarding effect of salvinorin A in zebrafish : κ-opioid and CB1-cannabinoid receptor involvement. In: Psychopharmacology. 2007 ; Vol. 190, No. 4. pp. 441-448.
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AU - Zani, Alessia

AU - Guerini-Rocco, Chiara

AU - Gori, Enzo

AU - Sala, Mariaelvina

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