title: Presynaptic dopamine D1 receptors attenuate excitatory and inhibitory limbic inputs to the shell region of the rat nucleus accumbens studied in vitro.
abstract: 1. Intracellular recordings were made from the shell region of the nucleus accumbens in an in vitro slice preparation. The mean resting membrane potential, input resistance, and action potential amplitude of these neurons were -76 +/- 1 mV, 87 +/- 5 M omega and 94 +/- 2 mV (N = 108), respectively. A sample of these neurons (N = 18) was identified as medium spiny neurons with the use of the biocytin-avidin labeling technique. 2. Electrical stimulation of the fornix, subcortical fibers, or neuropil within the nucleus accumbens shell itself elicited a depolarizing postsynaptic potential (PSP). Dopamine (10-100 microM) attenuated PSPs elicited by stimulation of all of these sites. In a paired-pulse stimulation protocol, dopamine was observed to enhance the facilitation of the test response with respect to the conditioning response. 3. The suppressive effect of dopamine was mimicked by the D1 receptor agonist SKF 82958 (10-30 microM), whereas the D2 receptor agonist quinpirole (10-30 microM) was ineffective. The action of dopamine was antagonized by the D1 receptor antagonist Sch 23390 (10-30 microM), but not by the D2 receptor antagonist sulpiride (10-50 microM) or various adrenergic receptor antagonists. 4. The PSP was usually composed of an excitatory postsynaptic potential (EPSP)-inhibitory postsynaptic potential (IPSP) sequence. Dopamine equally attenuated the excitatory and inhibitory component of the synaptic response. The attenuation of both EPSP and IPSP did not depend on membrane potential. 5. Dopamine effects on the resting membrane potential and input resistance were variable and did not correlate with changes in the PSP. Two further indications were found in favor of a presynaptic locus of dopaminergic modulation. First, the time course of the PSP was not altered during dopamine application. Second, dopamine did not attenuate depolarizations induced by bath-applied L-glutamate. In extracellular recordings, it was found that dopamine reduced the population spike but not the presynaptic fiber volley. 6. These findings strongly indicate that dopaminergic modulation of synaptic responses in neurons located in the accumbens shell region is mediated by presynaptic D1 receptors. Notably, dopamine does not exert a purely inhibitory effect on synaptic excitability in the nucleus accumbens, because it suppresses both the excitatory and inhibitory component of the synaptic response.
authors.affiliation: Department of Experimental Zoology, University of Amsterdam, Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: Pennartz
authors.forename: M J
authors.initials: MJ
authors.lastname: Dolleman-Van der Weel
authors.forename: S T
authors.initials: ST
authors.lastname: Kitai
authors.forename: F H
authors.initials: FH
authors.lastname: Lopes da Silva
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D004298:Dopamine / Q000494:pharmacology; D004525:Efferent Pathways / Q000502:physiology; D004594:Electrophysiology; D008032:Limbic System / Q000502:physiology*; D008297:Male; D009433:Neural Inhibition; D009714:Nucleus Accumbens / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
chemical_list: D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D004298:Dopamine