Document Detail

The effects of VTA NMDA receptor antagonism on reward-related learning and associated c-fos expression in forebrain.
MedLine Citation:
PMID:  20801158     Owner:  NLM     Status:  MEDLINE    
The mechanisms whereby reward-associated stimuli come to function as conditioned stimuli and acquire the capacity to activate the same neural regions activated by primary rewards (i.e., dopamine terminal regions) is not fully understood. We hypothesized that NMDA receptor stimulation in the VTA is necessary for the acquisition by a CS to both produce conditioned approach and activate dopamine terminal regions. Rats were tested in a conditioned approach protocol that consisted of light stimulus-food conditioning sessions (30 randomly presented light stimulus-food pellet pairings), a session with no stimuli or food and 1 session with only light stimulus (CS-only) presentations. Food trough head entries during the CS and just prior to the CS were recorded and a CS/pre-CS ratio indicating the conditioned approach response was calculated. Brain tissue was harvested after the CS-only session and processed for c-fos expression in prefrontal cortex area 2, nucleus accumbens core and shell and medial and lateral caudate. When bilateral intra-VTA microinjections of AP-5 (0, 0.25 or 0.5 μg) were made prior to each of the conditioning sessions the 0.5 μg AP-5 dose prevented the acquisition of conditioned approach; when 0.5 μg AP-5 injections were made prior to the CS-only test they failed to affect expression of the response. Also, 0.5 μg AP-5 prior to conditioning significantly reduced c-fos expression in response to the CS in nucleus accumbens core. These results suggest that VTA NMDA receptor stimulation is necessary for both the acquisition of reward-related learning and acquisition by the CS to activate dopamine terminal regions.
Robert Ranaldi; Karen Kest; Margaret R Zellner; Daniel Lubelski; Jonathan Muller; Yvonne Cruz; Michelle Saliba
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Publication Detail:
Type:  Journal Article     Date:  2010-08-27
Journal Detail:
Title:  Behavioural brain research     Volume:  216     ISSN:  1872-7549     ISO Abbreviation:  Behav. Brain Res.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-11-08     Completed Date:  2011-02-18     Revised Date:  2014-03-25    
Medline Journal Info:
Nlm Unique ID:  8004872     Medline TA:  Behav Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  424-32     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
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MeSH Terms
2-Amino-5-phosphonovalerate / pharmacology
Analysis of Variance
Catheters, Indwelling
Conditioning (Psychology) / drug effects*,  physiology
Excitatory Amino Acid Antagonists / pharmacology*
Prosencephalon / drug effects,  metabolism*
Proto-Oncogene Proteins c-fos / metabolism
Rats, Long-Evans
Receptors, N-Methyl-D-Aspartate / metabolism
Ventral Tegmental Area / drug effects*,  physiology
Reg. No./Substance:
0/Excitatory Amino Acid Antagonists; 0/Proto-Oncogene Proteins c-fos; 0/Receptors, N-Methyl-D-Aspartate; 76726-92-6/2-Amino-5-phosphonovalerate

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