Effects of l-tetrahydropalmatine on locomotor sensitization to oxycodone in mice

Aim: Recent studies have shown that 1-tetrahydropalmatine (l-THP), an active component of Corydolis yanhusuo, can inhibit the development of the conditional place preference induced by opioid receptor agonists, but the effects of l-THP on locomotor sensitivity induced by opioid receptor agonists have not been documented. In the present study, the effects of l-THP on locomotor sensitization to oxycodone, which is an opioid receptor agonist, were studied. Methods: Mice treated daily for 7 d with 5 mg/kg oxycodone and challenged with the same dose after 5 days of washout showed locomotor sensitization. In order to study the effects of l-THP on locomotor sensitization induced by oxycodone, l-THP was administered at doses of 6.25, 12.5, and 18.75 mg/kg, 40 min prior to treatment of oxycodone. Results: l-THP per se did not affect the locomotor activity at the doses of 6.25, 12.5, and 18.75 mg/kg, but could antagonize the hyperactivity induced by oxycodone (5 mg/kg). Co-administration of l-THP (18.75 mg/kg), 40 min prior to oxycodone, could inhibit the development of sensitization to oxycodone. In addition, l-THP (6.25, 12.5, and 18.75 mg/kg, ig) dose-dependently prevented the expression of oxycodone sensitization. Conclusion: These results suggested that l-THP could attenuate the locomotor-stimulating effects of oxycodone and inhibit the development and expression of oxycodone behavioral sensitization.