Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine

Jaakko Kopra, Marian Villarta-Aguilera, Mari Savolainen, Samo Weingerl, Timo T. Myöhänen, Saara Rannanpää, Michael Francis Salvatore, Jaan Olle Andressoo, T. Petteri Piepponen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Addictive drugs enhance dopamine release in the striatum, which can lead to compulsive drug-seeking after repeated exposure. Glial cell line-derived neurotrophic factor (GDNF) is an important regulator of midbrain dopamine neurons, and may play a mechanistic role in addiction-related behaviors. To elucidate the components of GDNF-signaling that contribute to addiction-related behaviors of place preference and its extinction, we utilized two genetically modified GDNF mouse models in an amphetamine-induced conditioned place preference (CPP) paradigm and evaluated how the behavioral findings correlate with dopamine signaling in the dorsal and ventral striatum. We utilized two knock-in mouse strains to delineate contributions of GDNF and Ret signaling using MEN2B mice (constitutively active GDNF receptor Ret), and GDNF hypermorphic mice (enhanced endogenous GDNF expression). The duration of amphetamine-induced CPP was greatly enhanced in MEN2B mice, but not in the GDNF hypermorphic mice. The enhanced duration of CPP was correlated with increased tyrosine hydroxylase (TH) expression and dopamine content in the ventral striatum. Together, our results suggest that downstream components of GDNF signaling, in this case Ret, may mediate persistent drug-seeking behavior through increased TH expression and dopamine levels in the mesolimbic dopamine neurons.

Original languageEnglish
Pages (from-to)221-230
Number of pages10
JournalNeuropharmacology
Volume128
DOIs
StatePublished - 1 Jan 2018

Fingerprint

Glial Cell Line-Derived Neurotrophic Factor
Amphetamine
Dopamine
Dopaminergic Neurons
Tyrosine 3-Monooxygenase
Glial Cell Line-Derived Neurotrophic Factor Receptors
Drug-Seeking Behavior
Dopamine Agents
Mesencephalon
Conditioning (Psychology)
Pharmaceutical Preparations
Mouse Gdnf protein

Keywords

  • Amphetamine
  • Conditioned place preference
  • Dopamine
  • GDNF
  • MEN2B
  • Striatum

Cite this

Kopra, J., Villarta-Aguilera, M., Savolainen, M., Weingerl, S., Myöhänen, T. T., Rannanpää, S., ... Piepponen, T. P. (2018). Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine. Neuropharmacology, 128, 221-230. https://doi.org/10.1016/j.neuropharm.2017.10.010
Kopra, Jaakko ; Villarta-Aguilera, Marian ; Savolainen, Mari ; Weingerl, Samo ; Myöhänen, Timo T. ; Rannanpää, Saara ; Salvatore, Michael Francis ; Andressoo, Jaan Olle ; Piepponen, T. Petteri. / Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine. In: Neuropharmacology. 2018 ; Vol. 128. pp. 221-230.
@article{b07ffec5af70419daadd7d1e6d2816d1,
title = "Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine",
abstract = "Addictive drugs enhance dopamine release in the striatum, which can lead to compulsive drug-seeking after repeated exposure. Glial cell line-derived neurotrophic factor (GDNF) is an important regulator of midbrain dopamine neurons, and may play a mechanistic role in addiction-related behaviors. To elucidate the components of GDNF-signaling that contribute to addiction-related behaviors of place preference and its extinction, we utilized two genetically modified GDNF mouse models in an amphetamine-induced conditioned place preference (CPP) paradigm and evaluated how the behavioral findings correlate with dopamine signaling in the dorsal and ventral striatum. We utilized two knock-in mouse strains to delineate contributions of GDNF and Ret signaling using MEN2B mice (constitutively active GDNF receptor Ret), and GDNF hypermorphic mice (enhanced endogenous GDNF expression). The duration of amphetamine-induced CPP was greatly enhanced in MEN2B mice, but not in the GDNF hypermorphic mice. The enhanced duration of CPP was correlated with increased tyrosine hydroxylase (TH) expression and dopamine content in the ventral striatum. Together, our results suggest that downstream components of GDNF signaling, in this case Ret, may mediate persistent drug-seeking behavior through increased TH expression and dopamine levels in the mesolimbic dopamine neurons.",
keywords = "Amphetamine, Conditioned place preference, Dopamine, GDNF, MEN2B, Striatum",
author = "Jaakko Kopra and Marian Villarta-Aguilera and Mari Savolainen and Samo Weingerl and My{\"o}h{\"a}nen, {Timo T.} and Saara Rannanp{\"a}{\"a} and Salvatore, {Michael Francis} and Andressoo, {Jaan Olle} and Piepponen, {T. Petteri}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.neuropharm.2017.10.010",
language = "English",
volume = "128",
pages = "221--230",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Ltd",

}

Kopra, J, Villarta-Aguilera, M, Savolainen, M, Weingerl, S, Myöhänen, TT, Rannanpää, S, Salvatore, MF, Andressoo, JO & Piepponen, TP 2018, 'Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine', Neuropharmacology, vol. 128, pp. 221-230. https://doi.org/10.1016/j.neuropharm.2017.10.010

Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine. / Kopra, Jaakko; Villarta-Aguilera, Marian; Savolainen, Mari; Weingerl, Samo; Myöhänen, Timo T.; Rannanpää, Saara; Salvatore, Michael Francis; Andressoo, Jaan Olle; Piepponen, T. Petteri.

In: Neuropharmacology, Vol. 128, 01.01.2018, p. 221-230.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine

AU - Kopra, Jaakko

AU - Villarta-Aguilera, Marian

AU - Savolainen, Mari

AU - Weingerl, Samo

AU - Myöhänen, Timo T.

AU - Rannanpää, Saara

AU - Salvatore, Michael Francis

AU - Andressoo, Jaan Olle

AU - Piepponen, T. Petteri

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Addictive drugs enhance dopamine release in the striatum, which can lead to compulsive drug-seeking after repeated exposure. Glial cell line-derived neurotrophic factor (GDNF) is an important regulator of midbrain dopamine neurons, and may play a mechanistic role in addiction-related behaviors. To elucidate the components of GDNF-signaling that contribute to addiction-related behaviors of place preference and its extinction, we utilized two genetically modified GDNF mouse models in an amphetamine-induced conditioned place preference (CPP) paradigm and evaluated how the behavioral findings correlate with dopamine signaling in the dorsal and ventral striatum. We utilized two knock-in mouse strains to delineate contributions of GDNF and Ret signaling using MEN2B mice (constitutively active GDNF receptor Ret), and GDNF hypermorphic mice (enhanced endogenous GDNF expression). The duration of amphetamine-induced CPP was greatly enhanced in MEN2B mice, but not in the GDNF hypermorphic mice. The enhanced duration of CPP was correlated with increased tyrosine hydroxylase (TH) expression and dopamine content in the ventral striatum. Together, our results suggest that downstream components of GDNF signaling, in this case Ret, may mediate persistent drug-seeking behavior through increased TH expression and dopamine levels in the mesolimbic dopamine neurons.

AB - Addictive drugs enhance dopamine release in the striatum, which can lead to compulsive drug-seeking after repeated exposure. Glial cell line-derived neurotrophic factor (GDNF) is an important regulator of midbrain dopamine neurons, and may play a mechanistic role in addiction-related behaviors. To elucidate the components of GDNF-signaling that contribute to addiction-related behaviors of place preference and its extinction, we utilized two genetically modified GDNF mouse models in an amphetamine-induced conditioned place preference (CPP) paradigm and evaluated how the behavioral findings correlate with dopamine signaling in the dorsal and ventral striatum. We utilized two knock-in mouse strains to delineate contributions of GDNF and Ret signaling using MEN2B mice (constitutively active GDNF receptor Ret), and GDNF hypermorphic mice (enhanced endogenous GDNF expression). The duration of amphetamine-induced CPP was greatly enhanced in MEN2B mice, but not in the GDNF hypermorphic mice. The enhanced duration of CPP was correlated with increased tyrosine hydroxylase (TH) expression and dopamine content in the ventral striatum. Together, our results suggest that downstream components of GDNF signaling, in this case Ret, may mediate persistent drug-seeking behavior through increased TH expression and dopamine levels in the mesolimbic dopamine neurons.

KW - Amphetamine

KW - Conditioned place preference

KW - Dopamine

KW - GDNF

KW - MEN2B

KW - Striatum

UR - http://www.scopus.com/inward/record.url?scp=85031825020&partnerID=8YFLogxK

U2 - 10.1016/j.neuropharm.2017.10.010

DO - 10.1016/j.neuropharm.2017.10.010

M3 - Article

C2 - 29031851

AN - SCOPUS:85031825020

VL - 128

SP - 221

EP - 230

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

ER -