the link that acantelopepope posted sums it up nicely.
anyway,
http://cercor.oxford...stract/11/5/452The interactions between N-methyl-D-aspartate (NMDA) and D1 dopamine receptors in the rat prefrontal cortex were examined using whole-cell recordings from pyramidal neurons. The effects of NMDA, the D1 agonist SKF38393, or both compounds combined were tested on measures of cell excitability. Both NMDA (10–100 µM) and SKF38393 (5–10 µM) independently increased the number of spikes and decreased the latency of the first spike evoked by intracellular depolarizing current pulses. Combining low doses of NMDA (5 µM) and SKF38393 (2 µM) resulted in a marked increase of cell excitability. This synergism was blocked by SCH23390, protein kinase A (PKA) inhibitors, and the Ca2+ chelator BAPTA, and reduced by nifedipine. These results indicate the presence of a dopamine– glutamate interaction in the prefrontal cortex at the postsynaptic level, by which D1 dopamine receptors may maintain NMDA- mediated responses in prefrontal cortical pyramidal neurons through both a PKA-dependent pathway and Ca2+-dependent mechanisms.
https://www.research..._memory_in_ratsDopamine (DA) and N-methyl-d-aspartate (NMDA) receptors seem to be critically involved in working memory processing in the medial prefrontal cortex (mPFC). Effects of NMDA receptors blockade on dopamine D(1) receptors activation in the mPFC on spatial working memory was investigated. Adult male Wistar rats, well trained in an eight-arm radial maze and bilaterally cannulated in the mPFC, received intracortical administrations of saline (SAL) or SKF-38393 (DA D(1) receptor agonist) followed, 10min later, by MK-801 (non-competitive NMDA receptor antagonist). They were tested in 1h delayed tasks after 5min of the second administration. SKF-38393 (0.56 and 1.8mug) was disruptive to working memory, increasing significantly the number of errors in the 1h post-delay performance when administered into the mPFC. MK-801, at doses with no significant effects alone (0.32 or 1.0mug), reduced significantly the disruptive effect of 0.56mug SKF-38393. These results showed that the disruptive effect of DA D(1) receptors activation in the mPFC on working memory was significantly reduced by an open-channel NMDA receptor blockade, suggesting that the processing of working memory in the mPFC involving DA D(1) receptors depend, at least in part, of NMDA receptors activity in this cortical area.
http://cat.inist.fr/...cpsidt=16083289The anterior cingulate cortex (ACC) plays a key role in pain processing. It has been reported that increased activity of glutamatergic projections into the ACC intensifies nociception; whereas dopaminergic projections inhibit it. The aim of this study was to evaluate the role of dopaminergic and NMDA systems of the ACC in the modulation of long-term nociception elicited by sciatic denervation in the rat. Score, onset and incidence of long-term nociception were measured by the autotomy behavior. The effects of a single microinjection into the ACC of different doses of dopamine (100 nM, 100 μM and 100 mM), a NMDA receptor antagonist (MK801 200 nM and 9.34 mM) and amantadine, a dopamine agonist and NMDA receptor antagonist (10, 100 and 1000 μM) were tested on long-term nociception. Dopamine diminished autotomy behavior in an inverse dose-dependent manner, with dopamine 100 nM as most effective concentration. MK801 and amantadine elicited a significant reduction on autotomy score. Prior injections of Dl and D2 receptor antagonists blocked the antinociceptive effects of amantadine on long-term nociceptive behavior. The present study suggests an interaction between dopaminergic and glutamatergic systems within the ACC in the genesis and maintenance of long-term nociception.
http://www.ncbi.nlm....les/PMC1762427/The formation of enduring internal representation of sensory information demands, in many cases, convergence in time and space of two different stimuli. The first conveys the sensory input, mediated via fast neurotransmission. The second conveys the meaning of the input, hypothesized to be mediated via slow neurotransmission. We tested the biochemical conditions and feasibility for fast (NMDA) and slow (dopamine) neurotransmission to converge on the Mitogen Activated Protein Kinase signaling pathways, crucial in several forms of synaptic plasticity, and recorded its effects upon synaptic transmission. We detected differing kinetics of ERK2 activation and synaptic strength changes in the CA1 for low and high doses of neurotransmitters in hippocampal slices. Moreover, when weak fast and slow inputs are given together, they converge on ERK2, but not on p38 or JNK, and induce strong short-term synaptic depression. Surprisingly, pharmacological analysis revealed that a probable site of such convergence is the NMDA receptor itself, suggesting it serves as a detector and integrator of fast and slow neurotransmission in the mature mammalian brain, as revealed by ERK2 activation and synaptic function.
i think this one could be relevant, too.
http://www.ncbi.nlm..../pubmed/89858911. The neurotransmitter dopamine is found throughout the hypothalamus both in cell bodies and in axons originating from intra- and extrahypothalamic sources. To study the mechanisms of action of dopamine on cultured rat hypothalamic neurons, particularly in relation to Ca2+ regulation, we used Ca2+ digital imaging with fura-2 and whole cell patch-clamp recording. We focused on the modulatory actions of dopamine on glutamate. 2. Dopamine administration had little or no independent effect on intracellular Ca2+. However, in the presence of tetrodotoxin to block action potentials and action-potential-dependent transmitter release, dopamine (10 microM for 2-3 min) caused an increase in glutamate-evoked Ca2+ rises in 22% of 64 neurons and depressed glutamate-evoked Ca2+ rises in an equal number of neurons. Shorter exposure to dopamine reduced the number of responding cells. 3. Dopamine application to neurons with an elevated Ca2+ due to synaptic release of glutamate (in the absence of tetrodotoxin) generally caused a decrease in Ca2+ levels (40% of 106 neurons), but sometimes increased cytosolic Ca2+ (10% of 106 neurons). That dopamine influenced cells differently in conditions of spontaneous activity compared with evoked activity may be due to dopamine effects on presynaptic receptors detected under conditions of ongoing synaptic release of glutamate. 4. Dopamine modulation of glutamate responses was detected at early stages of neuronal development (embryonic day 18 after 2 days in vitro) and also after 60 days in vitro. 5. The D1, D2, and D3 dopamine receptor agonists SKF38393, quinpirole, and 7-OH-DPAT (+/- 7 hydroxy-dipropylaminotetralin) caused a reduction in Ca2+ levels raised by endogenous glutamate release or evoked by exogenous glutamate application. 6. To block the actions of dopamine released by hypothalamic neurons, D1 and D2 dopamine receptor antagonists were used. As with dopamine, dopamine antagonists had no effect on intracellular Ca2+ during glutamate receptor blockade. In the absence of glutamate receptor block, the D1 antagonist SCH23390 (1 microM) reduced Ca2+ in responding cells; in contrast, the D2 antagonist eticlopride (1 microM) generated a delayed increase in Ca2+ levels. 7. Dopamine is known to activate second messengers through G proteins independent of changes in membrane potential or input resistance. Whole cell recording was used to demonstrate that, parallel to the modulation of Ca2+, dopamine exerted a dramatic change in glutamate-mediated electrical activity, generally depressing activity and hyperpolarizing the membrane potential (8 of 15 neurons). In a smaller number of neurons (5 of 15), dopamine enhanced glutamate-mediated excitatory activity. 8. Dopamine-evoked changes in membrane potential were in part mediated through modulation of glutamate actions. Dopamine depressed glutamate-evoked currents in a dose-dependent fashion, with Hill slopes in individual neurons ranging from 0.3 to 0.6. Dopamine could also evoke a direct hyperpolarizing action on hypothalamic neurons in the presence of tetrodotoxin or glutamate receptor blockers, at least in part by opening K+ channels. 9. Glutamate plays an important role as a primary excitatory transmitter within the hypothalamus. Our data support the hypothesis that a major mechanism of dopamine's influence on hypothalamic neurons involves the modulation of glutamate's excitatory action, mostly by inhibition. This is consistent with the hypothesis that modulation of glutamate activity may be an important mechanism of dopamine action throughout the nervous system.
i think this one will be the party wrecker:
http://jn.physiology...tract/87/4/2167D1/D5 Dopamine Receptors Stimulate Intracellular Calcium Release in Primary Cultures of Neocortical and Hippocampal Neurons. J. Neurophysiol. 87: 2167-2175, 2002. D1/D5 dopamine receptors in basal ganglia, hippocampus, and cerebral cortex modulate motor, reward, and cognitive behavior. Previous work with recombinant proteins revealed that in cells primed with heterologous Gq/11-coupled G-protein-coupled receptor (GPCR) agonists, the typically Gs-linked D1/D5 receptors can stimulate robust release of calcium from internal stores when coexpressed with calcyon. To learn more about the intracellular signaling mechanisms underlying these D1/D5 receptor regulated behaviors, we explored the possibility that endogenous receptors stimulate internal release of calcium in neurons. We have identified a population of neurons in primary cultures of hippocampus and neocortex that respond to D1/D5 dopamine receptor agonists with a marked increase in intracellular calcium (Ca) levels. The D1/D5 receptor stimulated responses occurred in the absence of extracellular Ca2+ indicating the rises in Ca involve release from internal stores. In addition, the responses were blocked by D1/D5 receptor antagonists. Further, the D1/D5 agonist-evoked responses were state dependent, requiring priming with agonists of Gq/11-coupled glutamate, serotonin, muscarinic, and adrenergic receptors or with high external K+ solution. In contrast, D1/D5 receptor agonist-evoked Ca2+ responses were not detected in neurons derived from striatum. However, D1/D5 agonists elevated cAMP levels in striatal cultures as effectively as in neocortical and hippocampal cultures. Further, neither forskolin nor 8-Br-cAMP stimulation following priming was able to mimic the D1/D5 agonist-evoked Ca2+ response in neocortical neurons indicating that increased cAMP levels are not sufficient to stimulate Ca release. Our data suggest that D1-like dopamine receptors likely modulate neocortical and hippocampal neuronal excitability and synaptic function via Ca2+ as well as cAMP-dependent signaling.
