Electrophysiological Consequences of D 2 and/or D 3 Receptor Knockout by Antisense Oligonucleotides in Nigrostriatal Dopaminergic Neurons

Mesencephalic dopaminergic neurons possess receptors for their own neurotransmitter, dopamine, at both somatodendritic as well as axon terminal regions. These receptors are termed autoreceptors and act to modulate dopaminergic synaptic transmission in two ways. Activation of the somatodendritic autoreceptors produces a membrane hyperpolarization by increasing a potassium conductance (Lacey, 1993) which leads to an inhibition of spontaneous activity (Groves et al., 1975). Activation of the terminal autoreceptors produces a decrease in terminal excitability which is presumed to reflect a membrane hyperpolarization (Tepper et al., 1985) which leads to a reduction in dopamine synthesis and in calcium- and impulse-dependent release of dopamine from nerve terminals (Starke et al., 1989; Wolf and Roth, 1987).