Characterization of dopamine receptors mediating inhibition of excitatory synaptic transmission in the rat hippocampal slice

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Abstract

1. The effect of dopamine (DA) on the excitatory synaptic transmission was studied in the CA1 neurons of rat hippocampal slices using intracellular recording technique. 2. Depolarizing excitatory postsynaptic potentials (EPSPs) were evoked by stimulation of the Schaffer collateral-commissural pathway. Superfusion of DA (0.03-1 μM) reversibly decreased the EPSP in a concentration-dependent manner and with an estimated IC50 of 0.3 μM. The sensitivity of postsynaptic neurons to the glutamate-receptor agonists, α- amino-3-hydroxy-5-methylisoxazole-4-propionic acid or N-methyl-D-aspartate was unchanged by DA (0.3 μM) pretreatment. In addition, DA (0.3 μM) increased the magnitude of paired-pulse facilitation, a phenomenon attributed to an increase in the amount of transmitter released in response to the second stimulus. 3. The reduction of DA (0.3 μM) on the EPSP was antagonized by sulpiride (1-10 nM), a selective D2-receptor antagonist. However, D1- receptor antagonist, SKF-83566 (1-10 μM), did not significantly affect the reduction of DA (0.3 μM) on the EPSP. 4. (±)-2-(N-Phenylethyl-N- propyl)amino-5-hydroxytetralin (1 μM), an agonist of D2 receptor, mimicked the inhibitory effect of DA on the EPSP. However, neither the D1-receptor agonist SKF-38393 (1 μM) nor the D3-receptor agonist PD-128,907 (1 μM) affected the EPSP. 5. Incubation of hippocampal slices with pertussis toxin (PTX, 5 μg/ml) for 12 h prevented the reduction of EPSP induced by DA (0.3 μM). 6. Rp-adenosine-3',5'-cyclic monophosphothioate (25 μM), a potent inhibitor of protein kinase A (PKA), alone decreased the amplitude of EPSP below baseline values and prevented the subsequent reduction by DA (0.3 μM). 7. These results indicate that DA at a low concentration (≤0.3 μM) reduces the excitatory response of hippocampal CA1 neurons after synaptic stimulation via the activation of presynaptic D2 receptors. The presynaptic action of DA is mediated by a PTX-sensitive G1-proteins-coupled to PKA pathway.

Original languageEnglish
Pages (from-to)1887-1895
Number of pages9
JournalJournal of Neurophysiology
Volume76
Issue number3
DOIs
Publication statusPublished - 1996 Sep

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

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