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Behavioural and neurochemical assessment of salvinorin A abuse potential in the rat

Abstract

Rationale

Salvinorin A is a recreational drug derived from Salvia divinorum, a sage species long used as an entheogen. While salvinorin A has potent hallucinogenic properties, its abuse potential has not been assessed consistently in controlled behavioural and neurochemical studies in rodents.

Objective

This study aimed to assess salvinorin A abuse potential by measuring its capacity to establish and maintain self-administration behaviour and to modify dopamine (DA) levels in the nucleus accumbens (NAcc) of rats.

Results

Male Lister Hooded (LH) and Sprague-Dawley (SD) rats were allowed to self-administer salvinorin A (0.5 or 1.0 μg/kg/infusion) intravenously 2 h/day for 20 days under a continuous schedule of reinforcement and lever pressing as operandum. LH rats discriminated between the active and inactive levers but did not reach the acquisition criterion for stable self-administration (≥12 active responses vs ≤5 inactive responses for at least 5 consecutive days). SD rats discriminated between the two levers at the lower dose only but, like LH rats, never acquired stable self-administration behaviour. Systemic salvinorin A increased extracellular DA in the NAcc shell of both LH (at ≥40 μg/kg) and SD rats (at ≥5 μg/kg), but injection into the ventral tegmental area (VTA) induced no significant change in NAcc DA concentration in LH rats and only brief elevations in SD rats.

Conclusions

Salvinorin A differs from other commonly abused compounds since although it affects accumbal dopamine transmission, yet it is unable, at least at the tested doses, to sustain stable intravenous self-administration behaviour.

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Acknowledgments

Funding for this study was provided by the Italian Ministry of University and Scientific Research (Progetti di Ricerca a rilevante Interesse Nazionale, PRIN 2006); the authors are grateful to Dr. Barbara Tuveri and Marta Tuveri for animal care and technical assistance. This manuscript is dedicated to the memory of Dr. Maria Sabrina Spano.

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Correspondence to Paola Fadda.

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Serra, V., Fattore, L., Scherma, M. et al. Behavioural and neurochemical assessment of salvinorin A abuse potential in the rat. Psychopharmacology 232, 91–100 (2015). https://doi.org/10.1007/s00213-014-3641-z

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Keywords

  • Salvinorin A
  • Drug abuse
  • Addiction
  • Self-administration
  • Dopamine
  • Microdialysis