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Ventral Midbrain NMDA Receptor Blockade: From Enhanced Reward and Dopamine Inactivation

Overview of attention for article published in Frontiers in Behavioral Neuroscience, August 2016
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Title
Ventral Midbrain NMDA Receptor Blockade: From Enhanced Reward and Dopamine Inactivation
Published in
Frontiers in Behavioral Neuroscience, August 2016
DOI 10.3389/fnbeh.2016.00161
Pubmed ID
Authors

Giovanni Hernandez, Marie-Pierre Cossette, Peter Shizgal, Pierre-Paul Rompré

Abstract

Glutamate stimulates ventral midbrain (VM) N-Methyl-D-Aspartate receptors (NMDAR) to initiate dopamine (DA) burst firing activity, a mode of discharge associated with enhanced DA release and reward. Blockade of VM NMDAR, however, enhances brain stimulation reward (BSR), the results can be explained by a reduction in the inhibitory drive on DA neurons that is also under the control of glutamate. In this study, we used fast-scan cyclic voltammetry (FSCV) in anesthetized animals to determine whether this enhancement is associated with a change in phasic DA release in the nucleus accumbens. Rats were implanted with a stimulation electrode in the dorsal-raphe (DR) and bilateral cannulae above the VM and trained to self-administer trains of electrical stimulation. The curve-shift method was used to evaluate the effect of a single dose (0.825 nmol/0.5 μl/side) of the NMDAR antagonist, (2R,4S)-4-(3-Phosphopropyl)-2-piperidinecarboxylic acid (PPPA), on reward. These animals were then anesthetized and DA release was measured during delivery of electrical stimulation before and after VM microinjection of the vehicle followed by PPPA. As expected, phasic DA release and operant responding depended similarly on the frequency of rewarding electrical stimulation. As anticipated, PPPA produced a significant reward enhancement. Unexpectedly, PPPA produced a decrease in the magnitude of DA transients at all tested frequencies. To test whether this decrease resulted from excessive activation of DA neurons, we injected apomorphine 20 min after PPPA microinjection. At a dose (100 μg s.c.) sufficient to reduce DA firing under control conditions, apomorphine restored electrical stimulation-induced DA transients. These findings show that combined electrical stimulation and VM NMDARs blockade induce DA inactivation, an effect that indirectly demonstrates that VM NMDARs blockade enhances reward by potentiating stimulation-induced excitation in the mesoaccumbens DA pathway.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 23%
Student > Ph. D. Student 4 18%
Student > Master 4 18%
Student > Bachelor 2 9%
Professor 1 5%
Other 2 9%
Unknown 4 18%
Readers by discipline Count As %
Neuroscience 7 32%
Psychology 5 23%
Medicine and Dentistry 3 14%
Agricultural and Biological Sciences 1 5%
Social Sciences 1 5%
Other 0 0%
Unknown 5 23%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 February 2022.
All research outputs
#14,353,367
of 23,090,520 outputs
Outputs from Frontiers in Behavioral Neuroscience
#1,866
of 3,212 outputs
Outputs of similar age
#195,128
of 339,428 outputs
Outputs of similar age from Frontiers in Behavioral Neuroscience
#21
of 43 outputs
Altmetric has tracked 23,090,520 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,212 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.3. This one is in the 40th percentile – i.e., 40% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 339,428 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 43 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.