Further characterization of the effects of BMY 14802 on dopamine neuronal activity

Further evaluation of the effects of BMY 14802 on dopamine (DA) neuronal activity in the rat substantia nigra pars compacta (A9) was conducted with single-unit recording and microiontophoresis in anesthetized rats. Microiontophoretic administration of BMY 14802 (sigma, serotonin (5-HT)-1A and alpha-1 adrenoceptor ligand) had no effect on DA neurons. Microiontophoretic administration of (+)-3-PPP (weak D2 agonist with high affinity for sigma receptors) and quinpirole (D2/D3 agonist) inhibited A9 DA neuronal activity. Co-iontophoresis or i.v. pretreatment with BMY 14802 had no effect on the current-response curves for the effects of microiontophoretic (+)-3-PPP or quinpirole on A9 DA neurons. Co-iontophoretic administration of (-)-sulpiride, a selective D2 antagonist, blocked the inhibitory effects of microiontophoretic (+)-3-PPP. The effects of BMY 14802 (0.25-8 mg/kg, i.v.) on DA neurons (increased firing rate, increased burst-firing, reduced regularity of firing pattern) were not altered by acute brain hemitransection, but were blocked by pretreatment with NAN-190, an antagonist of 5-HT-1A and alpha-1 receptors. The alpha-1 receptor antagonist, prazosin, did not block these effects of BMY 14802. In conclusion, the effects of BMY 14802 on DA neuronal firing rate and firing pattern are indirect, perhaps due in part to the occupation of 5-HT-1A receptors.