Membrane properties and response to opioids of identified dopamine neurons in the guinea pig hypothalamus

Abstract

The electrophysiological properties and opioid responsiveness of the dopamine-containing neurons in the arcuate nucleus of the guinea pig hypothalamus were examined. Dopamine-containing neurons, identified immunocytochemically by the presence of tyrosine hydroxylase, had a mean length-to-width profile of 14.9 +/- 4.4 x 11.5 +/- 3.1 microns (N = 14). The Na+ action potential of these neurons was of short duration, and induction of repetitive firing (20-50 Hz) caused an afterhyperpolarization of 6-9 mV in amplitude, with a decay half-time of approximately 1.5 sec. Dopamine-containing cells exhibited a low threshold spike, which induced 1-4 Na+ action potentials. This potential had a threshold close to -65 mV, could not be induced without prior hyperpolarization and was not sensitive to TTX. Dopamine-containing neurons also exhibited a time- and voltage-dependent inward current at potentials negative to -70 mV, and Cs+ blocked this conductance. The mu-opioid agonist Tyr-D-Ala-Gly-mePhe-Gly-ol hyperpolarized (14 +/- 3 mV) dopamine neurons via induction of an outward current (93 +/- 44 pA near the resting membrane potential) which had a reversal potential similar to that expected for a selective potassium conductance. TTX (1 microM) did not block the opioid effects. These results show that dopamine neurons of the arcuate nucleus differ in their intrinsic conductances and their responsiveness to opioids from other CNS dopaminergic neurons. Furthermore, opioid activation of a potassium conductance resulted in a direct hyperpolarization of dopamine neurons of the arcuate nucleus, and we suggest that this mechanism may underlie the effects of opioids on dopamine-mediated prolactin release.