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.

Dopaminergic modulation of dye coupling between neurons in the core and shell regions of the nucleus accumbens

“…In three cases, increasing the amplitude of stimulation elicited action potentials. These responses are consistent with those reported previously for shell neurons (Pennartz and Kitai, 199 1;Pennartz et al, 1992;O'Donnell and Grace, 1993a).…”

Dopamine gating of glutamatergic sensorimotor and incentive motivational input signals to the striatum

“…Since the non-NMDA glutamate activity is necessary before the NMDA receptor can become activated, this selective amplification of the NMDA response should selectively boost already-strong input signals, as might be expected when the striatal cell receives converging excitatory input from a large number of cortical cells [44]. (A full understanding of DA's modulatory role in the striatum will also require consideration of presynaptic DA/ glutamate interactions [40,43,91,119]. While this paper does not attempt to integrate this important and complex literature into the current discussion, it will be of interest in the future to determine whether and how these presynaptic interactions might contribute to a selective gating function).…”

Dopaminergic Modulation of Prefrontal Cortical Input to Nucleus Accumbens NeuronsIn Vivo

“…Synaptic responses in accumbens neurons driven by stimulation of either the amygdala or the hippocampus are attenuated by stimulation of the VTA or local iontophoretic application of dopamine in vivo (Yang and Mogenson, 1984;DeFrance et al, 1985;Yim and Mogenson, 1988). Excitatory accumbens responses to PFC stimulation are also decreased by direct application of dopaminergic receptor agonists in vitro (Pennartz et al, 1992;O'Donnell and Grace, 1994;Harvey and Lacey, 1996;Nicola et al, 1996). However, the effects of dopamine and/or activation of the ascending dopaminergic fibers on PFC synaptic responses have not yet been investigated in vivo.…”