Interactions of dopamine with glutamate- and GABA-mediated synaptic transmission in the rat entorhinal cortex in vitro.
We have studied the interactions between dopamine and glutamate-mediated transmission in the entorhinal cortex using intracellular recording in a slice preparation from the rat brain. High concentrations (0.1-1 mM) of dopamine had weak, direct effects on the membrane potential with predominantly hyperpolarizing responses in layer II neurons and depolarizing responses in layer V. Studies with the dopamine antagonists sulpiride (D2 antagonist, 10-50 microM) and SCH-23390 (D1 antagonist, 50 microM) indicated that the hyperpolarization by dopamine could be mediated by D2 receptors, although the pharmacology was not clear-cut. The depolarizing response was not affected by either D1 or D2 antagonists. Synaptic responses of layer II and layer V cells were complex, consisting of both inhibitory and excitatory potentials. In untreated slices, dopamine reduced all components of the synaptic responses. However, when components of the responses were pharmacologically isolated, only the excitatory, glutamate-mediated potentials were consistently affected and the GABAergic inhibitory potentials were more resistant to reduction by dopamine. Excitatory potentials mediated by both N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid receptors were reduced by dopamine, but the former were more strongly affected. Studies with antagonists suggested that the D1 receptor is more likely to be involved in the decrement of glutamate transmission. Thus, dopamine appears to modulate glutamate-mediated synaptic transmission in the entorhinal cortex, and it is conceivable that a disturbance in this interaction could be involved in the aetiology of schizophrenia.
Pralong
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University Department of Pharmacology, University of Oxford, UK.
Jones
R S
RS
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D018492:Dopamine Antagonists; D004594:Electrophysiology; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008032:Limbic System / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013469:Sulpiride / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D001552:Benzazepines; D018492:Dopamine Antagonists; D005971:Glutamates; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D013469:Sulpiride; D004298:Dopamine