ERK1/2 activation in rat ventral tegmental area by the mu-opioid agonist fentanyl: an in vitro study.
Opioid receptors in the ventral tegmental area, predominantly the mu-opioid receptors, have been suggested to modulate reinforcement sensitivity for both opioid and non-opioid drugs of abuse. The present study was conducted to study signal transduction proteins, which may mediate the functioning of mu-opioid receptors in the neurons of the ventral tegmental area. Therefore, brain slices of the ventral tegmental area were exposed in vitro to the specific mu-opioid agonist fentanyl and immunohistochemically stained for four different activated proteins using phospho-specific antibodies. Fentanyl dose-dependently activated extracellular signal-regulated protein in brain slices of the ventral tegmental area. This activation was reversible with naloxone. Furthermore, naloxone itself also activated extracellular signal-regulated protein kinase. Under the present conditions fentanyl did not affect extracellular signal-regulated protein kinase 1 and 2, Stat and cyclic AMP-response element-binding protein activity. The direct activation of extracellular signal-regulated protein kinase in ventral tegmental area slices by the mu-opioid agonist fentanyl may suggest a role of extracellular signal-regulated protein kinase in reward processes.
Lesscher
H M B
HM
Division of Pharmacology and Anatomy, Rudolf Magnus Institute for Neurosciences, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
Burbach
J P H
JP
van Ree
J M
JM
Gerrits
M A F M
MA
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005283:Fentanyl / Q000494:pharmacology*; D007150:Immunohistochemistry; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000201:enzymology*
D000701:Analgesics, Opioid; D017362:Cyclic AMP Response Element-Binding Protein; D017450:Receptors, Opioid, mu; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D020929:Mitogen-Activated Protein Kinase Kinases; D005283:Fentanyl