Back to Search
Start Over
Selective Activation of Striatal NGF-TrkA/p75NTR/MAPK Intracellular Signaling in Rats That Show Suppression of Methamphetamine Intake 30 Days following Drug Abstinence.
- Source :
-
The international journal of neuropsychopharmacology [Int J Neuropsychopharmacol] 2018 Mar 01; Vol. 21 (3), pp. 281-290. - Publication Year :
- 2018
-
Abstract
- Background: The continuing epidemic of methamphetamine addiction has prompted research aimed at understanding striatal dysfunctions potentially associated with long-term methamphetamine use.<br />Methods: Here, we investigated transcriptional and translational alterations in the expression of neurotrophic factors in the rat striatum at 30 days following methamphetamine self-administration and footshock punishment. Male Sprague-Dawley rats were trained to self-administer methamphetamine (0.1 mg/kg/injection, i.v.) or saline during twenty-two 9-hour sessions. Subsequently, rats were subjected to incremental footshocks for 13 additional methamphetamine self-administration sessions. This paradigm led to the identification of rats with shock-resistant and shock-sensitive phenotypes. Thirty days following the last footshock session, the dorsal striatum was dissected and processed for gene expression and protein analyses.<br />Results: PCR arrays revealed significant differences in neurotrophins and their receptors between the 2 phenotypes. Brain-derived neurotrophic factor and nerve growth factor protein levels were increased in the dorsal striatum of both shock-resistant and shock-sensitive rats. However, neurotrophic receptor tyrosine kinase 1 phosphorylation and nerve growth factor receptor protein expression were increased only in the shock-sensitive phenotype. Moreover, shock-sensitive rats showed increased abundance of several phosphorylated proteins known to participate in Ras/Raf/MEK/ERK signaling cascade including cRaf, ERK1/2, MSK1, and CREB.<br />Conclusions: These findings support the notion that animals with distinct phenotypes for methamphetamine intake in the presence of adverse consequences also display differential changes in an intracellular signaling cascade activated by nerve growth factor-TrkA/p75NTR interactions. Thus, the development of pharmacological agents that can activate nerve growth factor-dependent pathways may be a promising therapeutic approach to combat methamphetamine addiction.<br /> (© The Author 2017. Published by Oxford University Press on behalf of CINP.)
- Subjects :
- Animals
Disease Models, Animal
Electroshock
Extracellular Signal-Regulated MAP Kinases metabolism
Foot
Gene Expression drug effects
Male
Nerve Growth Factor metabolism
Nerve Tissue Proteins
Rats, Sprague-Dawley
Receptor, trkA metabolism
Receptors, Growth Factor
Receptors, Nerve Growth Factor metabolism
Self Administration
Signal Transduction drug effects
Amphetamine-Related Disorders metabolism
Central Nervous System Stimulants administration & dosage
Corpus Striatum drug effects
Corpus Striatum metabolism
Methamphetamine administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1469-5111
- Volume :
- 21
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The international journal of neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 29165617
- Full Text :
- https://doi.org/10.1093/ijnp/pyx105