D1/D5 dopamine receptor activation increases the magnitude of early long-term potentiation at CA1 hippocampal synapses.

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 approximately 10, 15, and 20%, respectively). This D1/D5 effect was mimicked by a low dose (10 microM) of the adenylyl cyclase activator forskolin. The D1/D5 antagonist (+)SCH 23390 reduced early LTP. In catecholamine-depleted slices, LTP was smaller by approximately 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.