Phospholipase Cgamma in distinct regions of the ventral tegmental area differentially modulates mood-related behaviors

Neurotrophic factor signaling pathways modulate cellular and behavioral responses to drugs of abuse. In addition, chronic exposure to morphine increases expression of phospholipase Cgamma1 (PLCgamma1) (a protein involved in neurotrophic signaling) in the ventral tegmental area (VTA), a neural substr...

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Bibliographic Details
Published in:The Journal of neuroscience 2003-08, Vol.23 (20), p.7569-7576
Main Authors: Bolaños, Carlos A, Perrotti, Linda I, Edwards, Scott, Eisch, Amelia J, Barrot, Michel, Olson, Valerie G, Russell, David S, Neve, Rachael L, Nestler, Eric J
Format: Article
Language:English
Subjects:
Affect
Animals
Behavior, Animal
Conditioning (Psychology)
Electric Stimulation
Genetic Vectors
Male
Maze Learning
Morphine - pharmacology
Narcotics - pharmacology
Phospholipase C gamma
Rats
Rats, Sprague-Dawley
Reward
Simplexvirus - genetics
Stress, Psychological - etiology
Sucrose - administration & dosage
Swimming
Type C Phospholipases - genetics
Type C Phospholipases - metabolism
Ventral Tegmental Area - anatomy & histology
Ventral Tegmental Area - enzymology
Ventral Tegmental Area - physiology
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Summary:Neurotrophic factor signaling pathways modulate cellular and behavioral responses to drugs of abuse. In addition, chronic exposure to morphine increases expression of phospholipase Cgamma1 (PLCgamma1) (a protein involved in neurotrophic signaling) in the ventral tegmental area (VTA), a neural substrate for many drugs of abuse. Using viral-mediated gene transfer to locally alter the activity of PLCgamma1, we show that overexpression of PLCgamma1 in rostral portions of the VTA (R-VTA) results in increased morphine place preference, whereas PLCgamma1 overexpression in the caudal VTA (C-VTA) results in avoidance of morphine-paired compartments. In addition, overexpression of PLCgamma1 in R-VTA causes increased preference for sucrose and increased anxiety-like behavior but does not affect responses to stress or nociceptive stimuli. In contrast, overexpression of PLCgamma1 in C-VTA decreases preference for sucrose and increases sensitivity to stress and nociceptive stimuli, although there was a tendency for increased anxiety-like behavior as seen for the R-VTA. These results show that levels of PLCgamma1 in the VTA regulate responsiveness to drugs of abuse, natural rewards, and aversive stimuli and point to the possibility that distinct topographical regions within the VTA mediate generally positive versus negative responses to emotional stimuli. Moreover, these data also support a role for drug-induced elevations in PLCgamma1 expression in the VTA in mediating long-term adaptations to drugs of abuse and aversive stimuli.
ISSN:1529-2401