Repeated reserpine treatment alters firing pattern and responses of substantia nigral dopamine neurons.

Repeated reserpine treatment (1 mg/kg x 6 days) increased the number of spontaneously active substantia nigra pars compacta (SNC) dopamine (DA) cells and altered the firing pattern to a more irregular one in locally anesthetized rats. The selective DA D1 receptor agonist, SKF 38393, although having little effect on SNC DA cells in normal rats, profoundly inhibited the firing rate of SNC DA cells in reserpinized rats. On the contrary, the DA D2 receptor agonist, N-0437, significantly inhibited the firing rate of SNC DA cells in control rats, however, the inhibition was not significantly altered by reserpine. The inhibitory effect of the mixed DA receptor agonist, apomorphine, was significantly enhanced after reserpine treatment. In addition, the inhibition of SNC DA cell firing produced by D1 and D2 receptor agonists in reserpinized rats was reversed only by their own subtype antagonists. These results suggest that repeated reserpine treatment renders SNC DA cells responsive to D1 receptor stimulation, and that D1 receptors play a more important role than D2 receptors in the supersensitivity of SNC DA cells induced by repeated reserpine treatment. The results also indicate that D1 and D2 receptor agonists inhibit SNC DA cell firing separately and synergically in reserpinized rats.