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 language | English |
|---|---|
| Pages (from-to) | 441-448 |
| Number of pages | 8 |
| Journal | Psychopharmacology |
| Volume | 190 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Mar 2007 |
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Keywords
- Conditioned place preference
- Nor-binalthorphimine
- Salvia divinorum
- SR 141716A
- Swimming behavior
- Zebrafish
ASJC Scopus subject areas
- Pharmacology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Hallucinatory and rewarding effect of salvinorin A in zebrafish
T2 - κ-opioid and CB1-cannabinoid receptor involvement
AU - Braida, Daniela
AU - Limonta, Valeria
AU - Pegorini, Simona
AU - Zani, Alessia
AU - Guerini-Rocco, Chiara
AU - Gori, Enzo
AU - Sala, Mariaelvina
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
KW - Conditioned place preference
KW - Nor-binalthorphimine
KW - Salvia divinorum
KW - SR 141716A
KW - Swimming behavior
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=33846799142&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846799142&partnerID=8YFLogxK
U2 - 10.1007/s00213-006-0639-1
DO - 10.1007/s00213-006-0639-1
M3 - Article
C2 - 17219220
AN - SCOPUS:33846799142
VL - 190
SP - 441
EP - 448
JO - Psychopharmacology
JF - Psychopharmacology
SN - 0033-3158
IS - 4
ER -