Role for GDNF in Biochemical and Behavioral Adaptations to Drugs of Abuse
| Autor: | Frank H. Collins, Daniel H. Wolf, Amelia J. Eisch, Liya Shen, Chad J. Messer, Kim Whisler, Eric J. Nestler, William A. Carlezon, David S. Russell, Heiner Westphal |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Narcotics Neuroscience(all) animal diseases media_common.quotation_subject Nerve Tissue Proteins Endogeny Motor Activity Pharmacology Article Rats Sprague-Dawley Mice Cocaine Dopamine Uptake Inhibitors mental disorders medicine Glial cell line-derived neurotrophic factor Animals Glial Cell Line-Derived Neurotrophic Factor Nerve Growth Factors Protein kinase A media_common Mice Knockout Morphine biology Illicit Drugs urogenital system General Neuroscience Addiction Ventral Tegmental Area Dopaminergic Rats Behavior Addictive Ventral tegmental area Neuroprotective Agents medicine.anatomical_structure Nerve growth factor nervous system biology.protein Psychology psychological phenomena and processes medicine.drug |
| Zdroj: | Neuron. 26:247-257 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/s0896-6273(00)81154-x |
| Popis: | The present study examined a role for GDNF in adaptations to drugs of abuse. Infusion of GDNF into the ventral tegmental area (VTA), a dopaminergic brain region important for addiction, blocks certain biochemical adaptations to chronic cocaine or morphine as well as the rewarding effects of cocaine. Conversely, responses to cocaine are enhanced in rats by intra-VTA infusion of an anti-GDNF antibody and in mice heterozygous for a null mutation in the GDNF gene. Chronic morphine or cocaine exposure decreases levels of phosphoRet, the protein kinase that mediates GDNF signaling, in the VTA. Together, these results suggest a feedback loop, whereby drugs of abuse decrease signaling through endogenous GDNF pathways in the VTA, which then increases the behavioral sensitivity to subsequent drug exposure. |
| Databáze: | OpenAIRE |
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