Linked Life Data

20192945

Source:http://linkedlifedata.com/resource/pubmed/id/20192945

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-11-2
pubmed:abstractText
Pleiotrophin (PTN), a neurotrophic factor with important roles in survival and differentiation of dopaminergic neurons, is up-regulated in the nucleus accumbens after amphetamine administration suggesting that PTN could modulate amphetamine-induced pharmacological or neuroadaptative effects. To test this hypothesis, we have studied the effects of amphetamine administration in PTN genetically deficient (PTN -/-) and wild type (WT, +/+) mice. In conditioning studies, we found that amphetamine induces conditioned place preference in both PTN -/- and WT (+/+) mice. When these mice were re-evaluated after a 5-day period without amphetamine administration, we found that WT (+/+) mice did not exhibit amphetamine-seeking behaviour, whereas, PTN -/- mice still showed a robust drug-seeking behaviour. In immunohystochemistry studies, we found that amphetamine (10 mg/kg, four times, every 2 hours) causes a significant increase of glial fibrillary acidic protein positive cells in the striatum of amphetamine-treated PTN -/- mice compared with WT mice 4 days after last administration of the drug, suggesting an enhanced amphetamine-induced astrocytosis in the absence of endogenous PTN. Interestingly, we found in concomitant in vitro studies that PTN (3 µM) limits amphetamine (1 mM)-induced loss of viability of PC12 cell cultures, effect that could be related to the ability of PTN to induce the phosphorylation of Akt and ERK1/2. To test this possibility, we used specific Akt and ERK1/2 inhibitors uncovering for the first time that PTN-induced protective effects against amphetamine-induced toxicity in PC12 cells are mediated by the ERK1/2 signalling pathway. The data suggest an important role of PTN to limit amphetamine-induced neurotoxic and rewarding effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1369-1600
pubmed:author
pubmed:copyrightInfo
© 2010 The Authors, Addiction Biology © 2010 Society for the Study of Addiction.
pubmed:issnType
Electronic
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
403-12
pubmed:meshHeading
pubmed-meshheading:20192945-Amphetamine, pubmed-meshheading:20192945-Amphetamine-Related Disorders, pubmed-meshheading:20192945-Animals, pubmed-meshheading:20192945-Carrier Proteins, pubmed-meshheading:20192945-Cell Survival, pubmed-meshheading:20192945-Conditioning, Classical, pubmed-meshheading:20192945-Corpus Striatum, pubmed-meshheading:20192945-Cytokines, pubmed-meshheading:20192945-Dopamine, pubmed-meshheading:20192945-Glial Fibrillary Acidic Protein, pubmed-meshheading:20192945-Gliosis, pubmed-meshheading:20192945-Mice, pubmed-meshheading:20192945-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:20192945-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:20192945-Motivation, pubmed-meshheading:20192945-Nucleus Accumbens, pubmed-meshheading:20192945-PC12 Cells, pubmed-meshheading:20192945-Phosphorylation, pubmed-meshheading:20192945-Proto-Oncogene Proteins c-akt, pubmed-meshheading:20192945-Rats, pubmed-meshheading:20192945-Signal Transduction
pubmed:year
2010
pubmed:articleTitle
The neurotrophic factor pleiotrophin modulates amphetamine-seeking behaviour and amphetamine-induced neurotoxic effects: evidence from pleiotrophin knockout mice.
pubmed:affiliation
Laboratory Pharmacology and Toxicology, Univ. San Pablo CEU, 28668 Boadilla del Monte, Madrid, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't