Effects of (-)-stepholidine on firing activity of dopamine neurons in ventral tegmental area of rats

Extracellular single-unit recording techniques were used to evaluate the effects of (-)-stepholidine (SPD) on the firing activity of ventral tegmental area (VTA) dopamine (DA) neurons. SPD reversed the DA agonist apomorphine (Apo)-induced inhibition of VTA DA cell firing rate (ED50 = 4.9, 4.5-5.3 micrograms.kg-1), and the reversal was more rapid than that of a classic DA antagonist haloperidol (Hal) (ED50 = 11.2, 9.1-13.8 micrograms.kg-1). Pretreatment with SPD or Hal 0.5 mg.kg-1 attenuated Apo-induced inhibition, and SPD rendered the VTA DA cells less sensitive to larger doses of Apo (1024-4096 micrograms.kg-1) than Hal did. Pharmacological analysis indicated that the effects of SPD were mainly mediated through D2 subtype receptors. In addition, SPD increased the firing rate of VTA DA cells, while higher doses (1.4, 0.6-3.3 mg.kg-1) of SPD dramatically inactivated 4/6 of the VTA DA cells sampled. This inhibition was considered to be due to depolarization inactivation. These results suggest that SPD is a DA receptor antagonist and can effectively block the D2 autoreceptors located in the VTA DA cells.