Effects of pertussis toxin on caudate neuron electrophysiology: studies with dopamine D1 and D2 agonists

The selective D1 and D2-agonists SKF-38393 and N-0437 respectively, were tested in caudate pretreated with PT. A paired recording paradigm was used where the contralateral untreated caudate served as a control. Micropipettes were used to locally apply SKF-38393 and N-0437 onto neurons in both control and PT-pretreated caudate. A significant attenuation of the responses to the D2 agonist were observed after PT administration. Only 1 out of 12 cells tested on the PT side demonstrated any response to locally applied N-0437, whereas 90% of the neurons responded to the drug on the control side. Neurons from both the PT-pretreated and control caudates responded to locally applied SKF-38393. In addition to the specific D1 and D2 receptor agonists, DA and the indirect dopamine agonist PCP were tested for changes in responsiveness. Dopamine was equally efficacious at both control and PT-pretreated caudate neurons, which suggest that dopamine locally applied from the micropipette can interact with the unperturbed D1 receptors in the PT-pretreated caudate. On the other hand, the response to PCP was significantly attenuated after PT administration, which suggest that endogenously released DA preferentially interacts with the D2 receptor subtype. Taken together these data suggest an important role for the D2 receptor in the physiology of dopamine responsiveness in the caudate nucleus.