Effects of salvinorin A on locomotor sensitization to D2/D3 dopamine agonist quinpirole

Neurosci Lett. 2008 Dec 3;446(2-3):101-4. doi: 10.1016/j.neulet.2008.09.035.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology
  • Animals
  • Benzeneacetamides / pharmacology
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism
  • Diterpenes, Clerodane / pharmacology*
  • Dopamine / metabolism
  • Dopamine Agents / pharmacology
  • Dopamine Agonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions / physiology
  • Drug Resistance / drug effects
  • Drug Resistance / physiology
  • Drug Synergism
  • Male
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Pyrrolidines / pharmacology
  • Quinpirole / pharmacology*
  • Rats
  • Rats, Long-Evans
  • Receptors, Dopamine D2 / agonists*
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3 / agonists*
  • Receptors, Opioid, kappa / agonists
  • Receptors, Opioid, kappa / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Analgesics
  • Benzeneacetamides
  • Diterpenes, Clerodane
  • Dopamine Agents
  • Dopamine Agonists
  • Pyrrolidines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Receptors, Opioid, kappa
  • Quinpirole
  • U 69593
  • salvinorin A
  • Dopamine