Journal of Neuroscience, Vol 2, 415-423, Copyright © 1982 by Society for Neuroscience
Dopamine action on hippocampal pyramidal cells
LS Benardo and DA Prince
Dopamine (DA) was applied to CA1 region pyramidal cells in slices of guinea
pig hippocampus maintained in vitro in order to examine its
electrophysiological effect on CNS neurons. DA induced hyperpolarization of
membrane potential and an increased conductance in 75% the 21 CA1 neurons
to which it was applied. DA also augmented the afterhyperpolarizations and
increased conductance which normally follow spike trains in these neurons.
These effects were not altered by intracellular injections of Cl- but were
blocked when slices were bathed in Mn2+ solutions. The Mn2+ blockade of
DA-induced hyperpolarizations could be overcome when large amounts of
agonists were applied. The DA effects were long lasting, were mimicked by
the dopamine agonists apomorphine and Epinine, and were blocked by the
dopamine antagonists flupenthixol and chlorpromazine. Extracellular or
intracellular application of cyclic AMP mimicked the effects of DA. The
results suggest that DA-induced hyperpolarization and conductance changes
are mediated by a Ca2+-activated K+ conductance. DA may increase the
intracellular Ca2+ concentration through effects on one of the Ca2+
buffering mechanisms. The long duration of these effects suggest that DA
works though some intracellular intermediary, perhaps cyclic AMP,
considering that the actions of cyclic AMP on membrane properties are
similar to those of DA. The dopaminergic projection to the hippocampus
should have a powerful inhibitory action, which would be most effective in
modulating the activities of neurons exhibiting high levels of
excitability, particularly cells involved in cyclical burst generation.
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