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Volume 16, Number 23,
Issue of December 1, 1996
pp. 7478-7486
Copyright ©1996 Society for Neuroscience
D1/D5 Dopamine Receptor Activation Increases the Magnitude of
Early Long-Term Potentiation at CA1 Hippocampal Synapses
Received July 3, 1996; revised Sept. 11, 1996; accepted Sept. 13, 1996.
Nonna A. Otmakhova and
John E. Lisman
Department of Biology and Volen Center for Complex Systems,
Brandeis University, Waltham, Massachusetts 02254
The role of the mesolimbic dopaminergic system in the reinforcement
of learning suggests that dopamine should be able to modulate activity-dependent synaptic plasticity. We have examined the effect of
D1/D5 agonists on early long-term potentiation (LTP) (40 min) in the
CA1 region of hippocampal slices. D1/D5 agonists (+)bromo-APB, 6-chloro-PB, and dihydrexidine increased the magnitude of LTP in a
synapse-specific manner (by ~10, 15, and 20%, respectively). This
D1/D5 effect was mimicked by a low dose (10 µM) of the
adenylyl cyclase activator forskolin. The D1/D5 antagonist (+)SCH 23390 reduced early LTP. In catecholamine-depleted slices, LTP was smaller by
~20-25% and could not be decreased further by D1/D5 antagonist. Under these conditions, D1/D5 agonist 6-chloro-PB and forskolin produced a larger enhancement of LTP (20-25%), restoring it to the
control level. At the same dose, dideoxyforskolin did not affect early
LTP. The D1/D5 agonist effect was completely blocked by the D1/D5
antagonist (+)SCH 23390. These results indicate that dopamine produces
a synapse-specific enhancement of early LTP through D1/D5 receptors and
cAMP.
Key words:
CA1;
cAMP;
catecholamine depletion;
D1/D5
dopamine receptors;
early LTP;
field EPSP;
forskolin;
hippocampus
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