Effects of salvinorin A on locomotor sensitization to D2/D3 dopamine agonist quinpirole.
Pieter Beerepoot, Vincent Lam, Alice Luu, Bernice Tsoi, Daniel Siebert, Henry Szechtman
Neuroscience letters December 3, 2008 DOI: 10.1016/j.neulet.2008.09.035 via PubMed
Summary
AI-generated from the abstractThe kappa opioid receptor agonist salvinorin A, the active compound in Salvia divinorum, can either increase or decrease locomotor sensitization caused by the dopamine agonist quinpirole, depending on dose. Rats received biweekly injections of quinpirole plus salvinorin A (0.04, 0.4, or 2.0 mg/kg) or the synthetic kappa agonist U69593 (0.3 mg/kg) for ten sessions. The highest salvinorin A dose and U69593 both potentiated sensitization; the middle dose had no effect; the lowest dose attenuated it. Structural differences between salvinorin A and U69593 do not affect potentiation, and salvinorin A can bidirectionally modulate dopamine agonist sensitization.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | quinpirole salvinorin A U69593 |
| Dose | 0.5 mg/kg quinpirole; 0.04, 0.4, or 2.0 mg/kg salvinorin A; 0.3 mg/kg U69593 |
| Duration | Biweekly for 10 injections |
| Key finding | Salvinorin A bidirectionally modulates quinpirole-induced locomotor sensitization in rats, with a high dose potentiating and a low dose attenuating it. |
Abstract
Locomotor sensitization induced by the dopamine agonist quinpirole can be potentiated by co-treatment with the synthetic kappa opioid agonist U69593. The identification of salvinorin A, an active component of the psychotropic sage Salvia divinorum, as a structurally different agonist of kappa-opioid receptors raised the question of whether this compound would similarly potentiate sensitization to quinpirole. Rats were co-treated with 0.5 mg/kg quinpirole and either salvinorin A (0.04, 0.4 or 2.0 mg/kg) or U69593 (0.3 mg/kg). Control groups were co-treated with vehicle and saline, vehicle and quinpirole (0.5 mg/kg), or saline and salvinorin A (0.4 mg/kg). Rats were injected biweekly for a total of 10 injections and locomotor activity measured after each treatment. Results showed that the highest dose of salvinorin A potentiated sensitization to quinpirole as did U69593, the middle salvinorin A dose had no effect on quinpirole sensitization, and the lowest dose of salvinorin A attenuated sensitization to quinpirole. These findings indicate that structural differences between salvinorin A and U69593 do not affect the potentiation of quinpirole sensitization. Moreover, the opposite effects of high and low salvinorin A doses suggest that salvinorin A can produce bidirectional modulation of sensitization to dopamine agonists.