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

Salvinorin A, the active hallucinogen in Salvia divinorum, does not sustain stable intravenous self-administration in rats, indicating low abuse potential. Male Lister Hooded and Sprague-Dawley rats were given the drug intravenously for 20 days; neither strain consistently pressed an active lever more than an inactive one, failing to meet the criteria for stable self-administration. Although salvinorin A increased dopamine levels in the nucleus accumbens shell when given systemically (at 40 μg/kg or higher in Lister Hooded rats and 5 μg/kg or higher in Sprague-Dawley rats), direct injection into the ventral tegmental area produced no significant dopamine change in Lister Hooded rats and only brief elevations in Sprague-Dawley rats. Thus, salvinorin A differs from commonly abused drugs: it affects dopamine transmission but cannot sustain self-administration behavior at the doses tested.

Study at a glance

Abstract

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. 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. 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. 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.