scholarly journals NMDA Receptor-Dependent Cholinergic Modulation of Mesolimbic Dopamine Cell Bodies: Neurochemical and Behavioral Studies

2018 ◽  
Vol 10 (3) ◽  
pp. 1497-1505 ◽  
Author(s):  
Marina Spanos ◽  
Xiaohu Xie ◽  
Julie Gras-Najjar ◽  
Stephanie C. White ◽  
Leslie A. Sombers
Keyword(s):  
Nmda Receptor ◽  
Mesolimbic Dopamine ◽  
Cholinergic Modulation ◽  
Behavioral Studies ◽  
Dopamine Cell

scholarly journals Lateral hypothalamic NMDA receptor subunits NR2A and/or NR2B mediate eating: immunochemical/behavioral evidence

1999 ◽  
Vol 276 (3) ◽  
pp. R880-R891 ◽  
Author(s):  
Arshad M. Khan ◽  
Margarita C. Currás ◽  
Jennifer Dao ◽  
Faizi A. Jamal ◽  
Chuck A. Turkowski ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Nmda Receptor ◽  
Second Messengers ◽  
Nmda Receptor Antagonists ◽  
Hypothalamic Area ◽  
Specific Antibodies ◽  
Lateral Hypothalamic ◽  
Behavioral Studies ◽  
Behavioral Evidence ◽  
Feeding Control

Cells within the lateral hypothalamic area (LHA) are important in eating control. Glutamate or its analogs, kainic acid (KA) and N-methyl-d-aspartate (NMDA), elicit intense eating when microinjected there, and, conversely, LHA-administered NMDA receptor antagonists suppress deprivation- and NMDA-elicited eating. The subunit composition of LHA NMDA receptors (NMDA-Rs) mediating feeding, however, has not yet been determined. Identifying this is important, because distinct second messengers/modulators may be activated by NMDA-Rs with differing compositions. To begin to address this, we detected LHA NR2A and NR2B subunits by immunoblotting and NR2B subunits by immunohistochemistry using subunit-specific antibodies. To help determine whether NMDA-Rs mediating feeding might contain these subunits, we conducted behavioral studies using LHA-administered ifenprodil, an antagonist selective for NR2A- and/or NR2B-containing NMDA-Rs at the doses we used (0.001–100 nmol). Ifenprodil maximally suppressed NMDA- and deprivation-elicited feeding by 63 and 39%, respectively, but failed to suppress KA-elicited eating, suggesting its actions were behaviorally specific. Collectively, these results suggest that LHA NMDA-Rs, some of which contribute to feeding control, are composed of NR2A and/or NR2B subunits, and implicate NR2A- and/or NR2B-linked signal transduction in feeding behavior.

scholarly journals Cholinergic modulation of mesolimbic dopamine function and reward

2011 ◽  
Vol 104 (1) ◽  
pp. 76-81 ◽  
Author(s):  
Gregory P. Mark ◽  
Shkelzen Shabani ◽  
Lauren K. Dobbs ◽  
Stephen T. Hansen
Keyword(s):  
Mesolimbic Dopamine ◽  
Cholinergic Modulation

Muscarinic and Nicotinic Presynaptic Modulation of EPSCs in the Nucleus Accumbens During Postnatal Development

2002 ◽  
Vol 88 (6) ◽  
pp. 3315-3330 ◽  
Author(s):  
Liming Zhang ◽  
Richard A. Warren
Keyword(s):  
Nucleus Accumbens ◽  
Nmda Receptor ◽  
Postnatal Development ◽  
Nicotinic Receptor ◽  
Nicotinic Receptors ◽  
Cholinergic Modulation ◽  
Bathing Medium ◽  
Cholinergic Agonists ◽  
Postsynaptic Currents ◽  
Presynaptic Mechanisms

We have studied the modulatory effects of cholinergic agonists on excitatory postsynaptic currents (EPSCs) in nucleus accumbens (nAcb) neurons during postnatal development. Recordings were obtained in slices from postnatal day 1 (P1) to P27 rats using the whole cell patch-clamp technique. EPSCs were evoked by local electrical stimulation, and all experiments were conducted in the presence of bicuculline methchloride in the bathing medium and with QX-314 in the recording pipette. Under these conditions, postsynaptic currents consisted of glutamatergic EPSCs typically consisting of two components mediated by AMPA/kainate (KA) and N-methyl-d-aspartate (NMDA) receptors. The addition of acetylcholine (ACh) or carbachol (CCh) to the superfusing medium resulted in a decrease of 30–60% of both AMPA/KA- and NMDA-mediated EPSCs. In contrast, ACh produced an increase (≈35%) in both AMPA/KA and NMDA receptor-mediated EPSCs when administered in the presence of the muscarinic antagonist atropine. These excitatory effects were mimicked by the nicotinic receptor agonist 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP) and blocked by the nicotinic receptor antagonist mecamylamine, showing the presence of a cholinergic modulation mediated by nicotinic receptors in the nAcb. The antagonistic effects of atropine were mimicked by pirenzepine, suggesting that the muscarinic depression of the EPSCs was mediated by M1/M4 receptors. In addition, the inhibitory effects of ACh on NMDA but not on AMPA/KA receptor-mediated EPSC significantly increased during the first two postnatal weeks. We found that, under our experimental conditions, cholinergic agonists produced no changes on membrane holding currents, on the decay time of the AMPA/KA EPSC, or on responses evoked by exogenous application of glutamate in the presence of tetrodotoxin, but they produced significant changes in paired pulse ratio, suggesting that their action was mediated by presynaptic mechanisms. In contrast, CCh produced consistent changes in the membrane and firing properties of medium spiny (MS) neurons when QX-314 was omitted from the recording pipette solution, suggesting that this substance actually blocked postsynaptic cholinergic modulation. Together, these results suggest that ACh can decrease or increase glutamatergic neurotransmission in the nAcb by, respectively, acting on muscarinic and nicotinic receptors located on excitatory terminals. The cholinergic modulation of AMPA/KA and NMDA receptor-mediated neurotransmission in the nAcb during postnatal development could play an important role in activity-dependent developmental processes in refining the excitatory drive on MS neurons by gating specific inputs.

Functional interaction of dopamine and glutamate in the nucleus accumbens in the regulation of locomotion

1993 ◽  
Vol 71 (5-6) ◽  
pp. 407-413 ◽  
Author(s):  
Michael Wu ◽  
Stefan M. Brudzynski ◽  
Gordon J. Mogenson
Keyword(s):  
Locomotor Activity ◽  
Nucleus Accumbens ◽  
Nmda Receptor ◽  
Aspartic Acid ◽  
Receptor Agonist ◽  
Dopamine Neurons ◽  
Mesolimbic Dopamine ◽  
Axon Terminals ◽  
6 Hydroxydopamine ◽  
Dose Dependent

The interaction of dopamine and glutamate in the nucleus accumbens in the regulation of locomotion was investigated. Microinjection of N-methyl-D-aspartic acid (NMDA, a glutamatergic NMDA receptor agonist) or α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA, a quisqualic receptor agonist which is a glutamatergic non-NMDA receptor agonist) into the nucleus accumbens caused a substantial increase in locomotor activity. This increase in locomotor activity was significantly reduced by prior administration of the dopamine D2 agonist quinpirole, but not the D1 agonist, SKF 38393, into the same brain sites. The reduction in locomotion produced by quinpirole was dose dependent. Eight days after the ventral tegmental area was lesioned with 6-hydroxydopamine to destroy the dopamine projection and the axon terminals of the mesolimbic dopamine neurons in nucleus accumbens, the hyperkinetic effects produced by injections of NMDA and AMPA into the nucleus accumbens were substantially reduced. These results suggested that the glutamate agonist induced locomotion is mediated by dopamine. Thus, it appears that NMDA- or AMPA-induced locomotion is due to the activation of glutamate receptors on the mesolimbic dopamine terminals in the nucleus accumbens which release dopamine and subsequently increase locomotion.Key words: nucleus accumbens, dopamine, glutamate, quinpirole, locomotion, N-methyl-D-aspartic acid, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid.

Sign in / Sign up

Export Citation Format

Share Document