Phospholipase Cγ in Distinct Regions of the Ventral Tegmental Area Differentially Modulates Mood-Related Behaviors

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.

doi:10.1523/jneurosci.23-20-07569.2003

Cited by 62Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeuropeptides and Animal Physiology

Phospholipase Cγ in Distinct Regions of the Ventral Tegmental Area Differentially Modulates Mood-Related Behaviors

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Bolaños, Carlos A., Perrotti, Linda I., Edwards, Scott, Eisch, Amelia J., Barrot, Michel, Olson, Valerie G., Russell, David S., Neve, Rachael L. +1 more·2003·The Journal of Neuroscience

DOI 10.1523/jneurosci.23-20-07569.2003PMC PMC6740761

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Abstract

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.

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Data obtained with viral technology indicate that the anterior and posterior VTA play different roles in conditioned place preference induced by systemic cocaine or opiate administration.
“Data obtained with viral technology also indicate that the anterior and posterior VTA play different roles in conditioned place preference induced by systemic cocaine or opiate administration”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Bolanos et al., 2003

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Authors: Bolaños, C. A., Perrotti, L. I., Edwards, S., Eisch, A. J., Barrot, M., Olson, V. G., Russell, D. S., Neve, R. L., & Nestler, E. J.
Affiliations: Harvard University (US)
ORCID: Perrotti, Linda I.
Edwards, Scott
Eisch, Amelia J.
Barrot, Michel
Olson, Valerie G.
Russell, David S.
Neve, Rachael L.
Nestler, Eric J.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2003-08-20
Volume: 23
Issue: 20
Pages: 7569-7576
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.23-20-07569.2003
PMC: PMC6740761
OpenAlex: W2115048492
Cited by: 62
References: 66
Citations by year: 2024: 1 · 2023: 1 · 2020: 1 · 2018: 1 · 2017: 5 · 2014: 7 · 2013: 2 · 2012: 2
FWCI: 2.31
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Funders: National Institute of Mental Health
National Institute on Drug Abuse (K08DA000302)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: phospholipase C-gamma1, ventral tegmental area, morphine, place preference, drug avoidance, sucrose preference, anxiety-like behavior, stress sensitivity, nociception, neurotrophic signaling, viral gene delivery
MeSH terms: Affect, Animals, Behavior, Animal, Conditioning, Psychological, Electric Stimulation, Genetic Vectors, Male, Morphine, Narcotics, Type C Phospholipases, Reward, Stress, Psychological, Sucrose, Swimming, Rats, Sprague-Dawley, Ventral Tegmental Area, Simplexvirus, Maze Learning, Rats, Phospholipase C gamma

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Phospholipase Cγ in Distinct Regions of the Ventral Tegmental Area Differentially Modulates Mood-Related Behaviors

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