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.
Otmakhova
N A
NA
Department of Biology and Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02254, USA.
Lisman
J E
JE
D000818:Animals; D002395:Catecholamines / Q000172:deficiency; D005576:Colforsin / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D050641:Receptors, Dopamine D5; D013569:Synapses / Q000502:physiology*
D002395:Catecholamines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C493607:Drd5 protein, rat; D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5; D005576:Colforsin