Ventral Tegmental Area Afferents and Drug-Dependent Behaviors

Oliva, Idaira; Wanat, Matthew J.

doi:10.3389/fpsyt.2016.00030

Cited by 50 publications

(26 citation statements)

References 237 publications

(280 reference statements)

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“…followed the same protocol and reported approximately 25% of NeuN-positive cells were also TH-positive 30 . The exact percentage of TH-positive neurons in the VTA is not known, but is speculated to be about 50–60% 31 ; therefore, we considered the estimated 25–30% of TH-positive neurons after fluorescent-activated cell sorting (FACS) to be adequate for the suggested experiment, consistent with other studies 30 , 32 . There was no significant difference in the number of collected DA neurons per VTA between the treatment groups since the saline-treated and nicotine-treated groups had 27.1% ± 3.7% and 28.5% ± 3.1% double-positive neurons from the total NeuN-positive neurons, respectively.…”

Section: Resultssupporting

confidence: 63%

Investigating the genetic profile of dopaminergic neurons in the VTA in response to perinatal nicotine exposure using mRNA-miRNA analyses

Keller

Dragomir

Fan

et al. 2018

Sci Rep

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Maternal smoking during pregnancy is associated with an increased risk of developmental, behavioral, and cognitive deficits. Nicotine, the primary addictive component in tobacco, has been shown to modulate changes in gene expression when exposure occurs during neurodevelopment. The ventral tegmental area (VTA) is believed to be central to the mechanism of addiction because of its involvement in the reward pathway. The purpose of this study was to build a genetic profile for dopamine (DA) neurons in the VTA and investigate the disruptions to the molecular pathways after perinatal nicotine exposure. Initially, we isolated the VTA from rat pups treated perinatally with either nicotine or saline (control) and collected DA neurons using fluorescent-activated cell sorting. Using microarray analysis, we profiled the differential expression of mRNAs and microRNAs from DA neurons in the VTA in order to explore potential points of regulation and enriched pathways following perinatal nicotine exposure. Furthermore, mechanisms of miRNA-mediated post-transcriptional regulation were investigated using predicted and validated miRNA-gene targets in order to demonstrate the role of miRNAs in the mesocorticolimbic DA pathway. This study provides insight into the genetic profile as well as biological pathways of DA neurons in the VTA of rats following perinatal nicotine exposure.

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Section: Resultssupporting

confidence: 63%

Investigating the genetic profile of dopaminergic neurons in the VTA in response to perinatal nicotine exposure using mRNA-miRNA analyses

Keller

Dragomir

Fan

et al. 2018

Sci Rep

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“…The posterior VTA was targeted due to its proposed role in the rewarding effects of many drugs of abuse [40]. However, due to the heterogeneity in GABAergic inputs to and local interneurons within the VTA [3], it is possible the extracellular GABA concentration may differ between subregions within the VTA. For example, a recent study used low-flow push–pull perfusion to measure the extracellular concentration of multiple neurotransmitters with high spatial resolution [65].…”

Section: Discussionmentioning

confidence: 99%

“…The ventral tegmental area (VTA) is a brain region involved in reward processing, aversion and the development of some drug-dependent behaviors [1–3]. Inhibitory signaling in the VTA is altered by many drugs of abuse and γ-aminobutyric acid (GABA) neurons have an emerging role in regulating reward and aversive learning [4–6].…”

Section: Introductionmentioning

confidence: 99%

GABA Uptake Inhibition Reduces In Vivo Extraction Fraction in the Ventral Tegmental Area of Long Evans Rats Measured by Quantitative Microdialysis Under Transient Conditions

Zandy

Gonzales

2017

Neurochem Res

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Inhibitory signaling in the ventral tegmental area (VTA) is involved in the mechanism of action for many drugs of abuse. Although drugs of abuse have been shown to alter extracellular γ-aminobutyric acid (GABA) concentration in the VTA, knowledge on how uptake mechanisms are regulated in vivo is limited. Quantitative (no-net-flux) microdialysis is commonly used to examine the extracellular concentration and clearance of monoamine neurotransmitters, however it is unclear whether this method is sensitive to changes in clearance for amino acid neurotransmitters such as GABA. The purpose of this study was to determine whether changes in GABA uptake are reflected by in vivo extraction fraction within the VTA. Using quantitative (no-net-flux) microdialysis adapted for transient conditions, we examined the effects of local perfusion with the GABA uptake inhibitor, nipecotic acid, in the VTA of Long Evans rats. Basal extracellular GABA concentration and in vivo extraction fraction were 44.4 ± 1.9 nM (x-intercepts from 4 baseline regressions using a total of 24 rats) and 0.19 ± 0.01 (slopes from 4 baseline regressions using a total of 24 rats), respectively. Nipecotic acid (50 μM) significantly increased extracellular GABA concentration to 170 ± 4 nM and reduced in vivo extraction fraction to 0.112 ± 0.003. Extraction fraction returned to baseline following removal of nipecotic acid from the perfusate. Conventional microdialysis substantially underestimated the increase of extracellular GABA concentration due to nipecotic acid perfusion compared with that obtained from the quantitative analysis. Together, these results show that inhibiting GABA uptake mechanisms within the VTA alters in vivo extraction fraction measured using microdialysis and that in vivo extraction fraction may be an indirect measure of GABA clearance.

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“…Addiction to substances of abuse is thought to be caused by functional changes in a neural network implicated in emotions, learning and cognitive control (Robinson & Berridge, ; Goldstein & Volkow, ; Koob, ; Piazza & Deroche‐Gamonet, ; Volkow & Morales, ; Everitt & Robbins, ) as a result of prolonged exposure to drugs (Deroche‐Gamonet et al ., ; Vanderschuren & Everitt, ; Pelloux et al ., ; Jonkman et al ., ; Vanderschuren & Ahmed, ; Limpens et al ., ). Brain structures widely implicated in addiction include the prefrontal cortex, striatum, amygdala and the ventral tegmental area (VTA) (Jentsch & Taylor, ; Feil et al ., ; Koob & Volkow, ; Hearing et al ., ; Everitt & Robbins, ; Oliva & Wanat, ). More recently, studies have begun to investigate the role of the lateral habenula (LHb) in addictive behavior, and it has been suggested that this structure is important for the aversive aspects of drug intake (Jhou et al ., ; Meye et al ., ; Shelton et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous neuronal activity in the lateral habenula after short‐ and long‐term cocaine self‐administration in rats

Gao

Groenewegen

Vanderschuren³

et al. 2017

Eur J of Neuroscience

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Cocaine addiction is thought to be the result of drug-induced functional changes in a neural network implicated in emotions, learning and cognitive control. Recent studies have implicated the lateral habenula (LHb) in drug-directed behavior, especially its aversive aspects. Limited cocaine exposure has been shown to alter neuronal activity in the LHb, but the impact of long-term drug exposure on habenula function has not been determined. Therefore, using c-fos as a marker, we here examined neuronal activity in LHb in rats that self-administered cocaine for either 10 or 60 days. Both the density of labeled cells and the cellular labeling intensity were measured in the lateral (LHbL) and medial (LHbM) parts of LHb. After 10 days of cocaine self-administration, both the density and intensity of c-fos-positive cells were significantly increased in LHbL, but not LHbM, while after 60 days, an increased density (but not intensity) of labeled neurons in both LHbL and LHbM was observed. Most c-fos-labeled neurons were glutamatergic. In addition, we found increased GAD65 expression after 10 but not 60 days of cocaine self-administration in the rostral mesencephalic tegmental nucleus. These data shed light on the complex temporal dynamics by which cocaine selfadministration alters activity in LHb circuitry, which may play an important role in the descent to compulsive drug use as a result of prolonged cocaine-taking experience.

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Ventral Tegmental Area Afferents and Drug-Dependent Behaviors

Cited by 50 publications

References 237 publications

Investigating the genetic profile of dopaminergic neurons in the VTA in response to perinatal nicotine exposure using mRNA-miRNA analyses

Investigating the genetic profile of dopaminergic neurons in the VTA in response to perinatal nicotine exposure using mRNA-miRNA analyses

GABA Uptake Inhibition Reduces In Vivo Extraction Fraction in the Ventral Tegmental Area of Long Evans Rats Measured by Quantitative Microdialysis Under Transient Conditions

Heterogeneous neuronal activity in the lateral habenula after short‐ and long‐term cocaine self‐administration in rats

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