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

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Kopra , J , Villarta-Aguilera , M , Savolainen , M , Weingerl , S , Myohänen , T T , Rannanpää , S , Salvatore , M E , Andressoo , J-O & Piepponen , T P 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

Title: Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine
Author: Kopra, Jaakko; Villarta-Aguilera, Marian; Savolainen, Mari; Weingerl, Samo; Myohänen, Timo T.; Rannanpää, Saara; Salvatore, Michael E.; Andressoo, Jaan-Olle; Piepponen, T. Petteri
Contributor organization: Faculty of Pharmacy
Division of Pharmacology and Pharmacotherapy
Regenerative pharmacology group
Drug Research Program
Medicum
Institute of Biotechnology
Timo Petteri Piepponen / Principal Investigator
PREP in neurodegenerative disorders
Date: 2018-01
Language: eng
Number of pages: 10
Belongs to series: Neuropharmacology
ISSN: 0028-3908
DOI: https://doi.org/10.1016/j.neuropharm.2017.10.010
URI: http://hdl.handle.net/10138/309005
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. (C) 2017 Elsevier Ltd. All rights reserved.
Subject: Amphetamine
Conditioned place preference
Dopamine
GDNF
MEN2B
Striatum
NEUROTROPHIC FACTOR
SUBSTANTIA-NIGRA
BRAIN
MICE
NEURONS
DRUGS
ADDICTION
BEHAVIOR
ABUSE
3112 Neurosciences
317 Pharmacy
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion


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