Abstract

The kappa-opioid system (KOP) is the key in drug abuse. Of all the compounds isolated from Salvia divinorum (S. divinorum), salvinorin-A (Sal-A) is predominant. Further, Sal-A is the only compound within S. divinorum which is reported to have psychoactive properties as a powerful kappa-opioid receptor (KOPr) agonist. Based on the key role of the KOP system in the consumption of drugs, S. divinorum extract (SDE) and Sal-A may modify the alcohol intake in Wistar rats. Assessing voluntary alcohol intake as a drug consummatory behavior, food intake as natural reward behavior and tonic immobility as indicative of anxiety-like behavior, the present study sought to identify the role of both SDE and Sal-A in the Wistar rat model. Forty-eight adult male rats were randomly divided into six groups: control, alcohol naive and vehicle, alcohol-naive and SDE, alcohol-naive and Sal-A, alcohol-consumption and vehicle, alcohol-consumption and SDE, and alcohol-consumption and Sal-A. Alcohol and food intake were assessed for two weeks. In the middle of these two weeks, vehicle, SDE (containing ~1 mg/kg of Sal-A) or Sal-A was injected intraperitoneally once a day for a week. Tonic immobility testing was performed once. The administration of SDE produced a significant increase in voluntary alcohol intake especially in rats with a history of forced alcohol consumption from a juvenile age, Sal-A elicited an increase in alcohol intake in animals with or without previous alcohol exposure, SDE and Sal-A prolonged the tonic immobility duration and decreased food intake. In conclusion, S. divinorum or Sal-A stimulated alcohol consumption in rats with a history of alcohol intake and independent of previous exposure respectively, also SDE or Sal-A elicited an anorexigenic effect, and increased tonic immobility as indicative of anxious-like behavior. The kappa-opioid system (KOP) is the key in drug abuse. Of all the compounds isolated from Salvia divinorum (S. divinorum), salvinorin-A (Sal-A) is predominant. Further, Sal-A is the only compound within S. divinorum which is reported to have psychoactive properties as a powerful kappa-opioid receptor (KOPr) agonist. Based on the key role of the KOP system in the consumption of drugs, S. divinorum extract (SDE) and Sal-A may modify the alcohol intake in Wistar rats. Assessing voluntary alcohol intake as a drug consummatory behavior, food intake as natural reward behavior and tonic immobility as indicative of anxiety-like behavior, the present study sought to identify the role of both SDE and Sal-A in the Wistar rat model. Forty-eight adult male rats were randomly divided into six groups: control, alcohol naive and vehicle, alcohol-naive and SDE, alcohol-naive and Sal-A, alcohol-consumption and vehicle, alcohol-consumption and SDE, and alcohol-consumption and Sal-A. Alcohol and food intake were assessed for two weeks. In the middle of these two weeks, vehicle, SDE (containing ~1 mg/kg of Sal-A) or Sal-A was injected intraperitoneally once a day for a week. Tonic immobility testing was performed once. The administration of SDE produced a significant increase in voluntary alcohol intake especially in rats with a history of forced alcohol consumption from a juvenile age, Sal-A elicited an increase in alcohol intake in animals with or without previous alcohol exposure, SDE and Sal-A prolonged the tonic immobility duration and decreased food intake. In conclusion, S. divinorum or Sal-A stimulated alcohol consumption in rats with a history of alcohol intake and independent of previous exposure respectively, also SDE or Sal-A elicited an anorexigenic effect, and increased tonic immobility as indicative of anxious-like behavior.

Highlights

  • Salvia divinorum (S. divinorum) (Lamiaceae family; formerly Labiatae) contains diterpenes such as salvinorin A and B, as well as additional diterpenoids, divinatorines (A-F), salvidivines (A-D), salvinicins (A and B) and nine additional salvinorins (C-J) (Keasling and Zjawiony, 2016)

  • Due to the heterogeneity of the findings regarding the behavioral profile of S. divinorum and Sal‐A administration, the present study aimed to provide clear insights into the effects of S. divinorum extract (SDE) containing Sal‐A as the main pharmacological active constituent, and Sal‐A itself, on alcohol and food intake as well as tonic immobility

  • We found that alcohol intake plus vehicle injection (ACVEH), ACSDE, and alcohol intake and Sal‐A injection (ACSALA) differ significantly from ANVEH, ANSDE, and ANSALA from day‐1 to day‐14

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Summary

Introduction

Salvia divinorum (S. divinorum) (Lamiaceae family; formerly Labiatae) contains diterpenes such as salvinorin A and B, as well as additional diterpenoids, divinatorines (A-F), salvidivines (A-D), salvinicins (A and B) and nine additional salvinorins (C-J) (Keasling and Zjawiony, 2016). Salvinorin A (Sal‐A) is the only known psychoactive/hallucinogenic constituent of S. divinorum. Sal‐A is a unique furanolactone neoclerodane diterpene which acts as a potent non‐nitrogenous selective kappa‐opioid receptor (KOPr) agonist (Roth et al, 2002; Willmore‐Fordham et al, 2007). Increases alcohol/anxiety and decreases food intake 35 serotonergic system (5‐HT2A) (Roth et al, 2002; Prisinzano, 2005; Johnson et al, 2011). Due to its powerful hallucinogenic effects, S. divinorum is often co‐consumed (smoking) with alcohol. Sal‐A isolated from S. divinorum leaves produced a unique profile of subjective effects in humans, similar to other classic hallucinogens (Johnson et al, 2011). A single dose of Sal‐A (200-500 μg) results in strong, yet brief (5-10 min), hallucinogenic effects and a change in perception (Siebert, 1994)

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