Inhibitory and excitatory effects of dopamine on Aplysia neurones

1. Electrophoretic application of dopamine (DA) on Aplysia neurones elicits both excitatory and inhibitory effects, which in many cases are observed in the same neurone, and often result in a biphasic response.2. The DA receptors are localized predominantly on the axons. Desensitization, which occurs after repeated injections or with bath application of DA, is more marked for excitatory responses.3. Tubocurarine and strychnine block the DA excitatory responses without affecting the inhibitory ones, which can be selectively blocked by ergot derivatives. It is concluded that the excitatory and inhibitory effects are mediated by two distinct receptors.4. The two DA receptors can be pharmacologically separated from the three ACh receptors described in the same nervous system.5. In some neurones the dopamine inhibitory responses can be inverted by artificial hyperpolarization of the membrane at the potassium equilibrium potential, E(K), indicating that dopamine causes a selective increase in potassium permeability.6. In other neurones the reversal potential of dopamine inhibitory responses is at a more depolarized level than E(K), but can be brought to E(K) by pharmacological agents known to block the receptors mediating the excitatory effects of DA.7. In still other neurones, the hyperpolarization induced by DA cannot be inverted in normal conditions, but a reversal can be induced by ouabain or by the substitution of external sodium by lithium. These results are discussed in terms of an hypothesis in which dopamine increases the potassium permeability of a limited region of the axonal membrane.8. It is concluded that a selective increase in potassium permeability probably accounts for all dopamine inhibitory effects in the neurones studied.