ERK1/2 activation in rat ventral tegmental area by the μ-opioid agonist fentanyl: An in vitro study

Opioid receptors in the ventral tegmental area, predominantly the μ-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 μ-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 μ-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 μ-opioid agonist fentanyl may suggest a role of extracellular signal-regulated protein kinase in reward processes.