Depression of excitatory cortico-nucleus accumbens synaptic transmission in rat brain slices by dopamine, but not adenosine, depends upon intracortical mechanisms

Abstract

Extracellular field potentials, evoked by stimulation of the cortico-NAcc border, were recorded from the nucleus accumbens (NAcc) in horizontal slices of rat ventral forebrain. The peak amplitude of the population spike/excitatory postsynaptic potential complex (PEC, N2 component) was reduced by 78+/-2% ( n=44) by the antagonist of AMPA-type glutamate receptors, 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX, 10 microM). Dopamine (100 microM) reversibly depressed the peak amplitude of the PEC by 40+/-3% ( n=44). The GABA(A) receptor antagonists picrotoxin (10, 30 microM), or bicuculline methiodide (BMI, 20 microM), significantly reduced the PEC depression caused by dopamine (100 microM) to 9+/-3% ( n=20), 12+/-7% ( n=8) and 13+/-3% ( n=4) of control respectively, which, in the case of BMI, was reversible on washout of BMI. In slices with the frontal cortex removed (decorticated), dopamine (100 microM) was without effect on the PEC ( n=14). In contrast, the inhibition of the PEC by adenosine (by 40+/-9% in control, n=4), which was blocked by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 200 nM), was unaffected by picrotoxin (50 microM, n=4), and persisted in decorticated slices, albeit increased to 88+/-2% ( n=4) of control. These results indicate that the depression of the cortico-NAcc synaptic transmission by dopamine in this preparation is due to an action in frontal, possibly piriform, cortex, which may involve modulation of intracortical GABAergic circuitry. In contrast, depression by adenosine is consistent with a presynaptic action via A1 receptors on intra-NAcc glutamate-releasing terminals, although there may be an additional action of adenosine within the cortex that also influences the cortico-NAcc PEC.

Dopamine-mediated MK-801-induced elevation in food-based extinction responding in rats and associated changes in region-specific phosphorylated ERK

“…The piriform cortex shows a glutamatergic projection to the nucleus accumbens (McGeorge and Faull 1989) whereby stimulation of AMPA receptors in the nucleus accumbens mediates an excitatory effect (Buckby and Lacey 2001). With a blunting of piriform activity produced by MK-801, piriform inputs to the nucleus accumbens would be attenuated, resulting in a shift in the excitatory control of accumbens activity by other means, such as the IL-VTA DA circuit or a glutamatergic NMDA receptor-independent input from the amygdala (Jackson and Moghaddam 2001;Sesack and Grace 2010).…”

Enaminones and norepinephrine employ convergent mechanisms to depress excitatory synaptic transmission in the rat nucleus accumbens in vitro

“…To further characterize the pharmacology of enaminones, we sought to determine if these compounds interacted with NE and DA to produce their reported anticonvulsant effects. This is especially important as, similar to E139, NE and DA also depress EPSCs in this nucleus (Harvey & Lacey, 1996, 1997; Nicola & Malenka, 1997; Buckby & Lacey, 2001; Kombian et al ., 2003). Taking advantage of this presence of both adrenergic and dopaminergic actions in this nucleus, we tested the hypothesis that E139 interacts with adrenergic and/or dopaminergic mechanisms in the NAc to produce the reported excitatory synaptic depression that may contribute to its in vivo anticonvulsant effects.…”

Cholecystokinin activates CCKB receptors to excite cells and depress EPSCs in the rat rostral nucleus accumbens in vitro

“…While the neurochemical and behavioural effects of CCK have been extensively studied, its cellular and synaptic effects are not well characterized. Electrophysiologically, DA is reported to act either directly on D1‐like dopamine receptors located on glutamatergic terminals to decrease synaptic transmission (Harvey & Lacey, 1996; Nicola & Malenka, 1997) or indirectly on these same receptors located on medium spiny neurones to cause the generation of adenosine, which then acts on presynaptic glutamatergic terminals to decrease EPSCs (Harvey & Lacey, 1997; Buckby & Lacey, 2001; Kombian et al 2003 a ). How CCK may influence these effects of DA is not known.…”