Extracellular signal-regulated kinase activation in the amygdala mediates elevated plus maze behavior during opioid withdrawal.
This study examined whether activation of extracellular signal-regulated kinase (ERK) contributes to the increased open-arm time observed in the elevated plus maze (EPM) during opioid withdrawal. We applied SL327, a selective ERK kinase (MEK) inhibitor, to specific limbic areas and examined the effect on EPM behaviors of controls and during naloxone-precipitated morphine withdrawal. We next confirmed that ERK activation increased in limbic areas of mice undergoing naloxone-precipitated morphine withdrawal. Direct injection of SL327 into the amygdala blocked the withdrawal-induced increase in open-arm time; however, injecting SL327 into the septum had no effect. Consistent with these results, both 0.2 and 2 mg/kg naloxone increased ERK activation in the central amygdala of morphine-dependent mice. In drug-naive mice, 2 mg/kg naloxone, but not 0.2 mg/kg, increased ERK activation in the central amygdala. During withdrawal, increased ERK activation was also observed in the lateral septum. In the locus coeruleus, a significant increase was observed only in morphine-dependent mice receiving 2 mg/kg, but not 0.2 mg/kg naloxone. In conclusion, ERK activation in limbic areas is likely involved in both the aversive properties of naloxone and in the affective/emotional symptoms of opioid withdrawal, including mediating EPM behaviors.
Hofford
Rebecca S
RS
Department of Psychology, Behavioral and Cellular Neuroscience, Texas A&M University, College Station, Texas, USA.
Hodgson
Stephen R
SR
Roberts
Kris W
KW
Bryant
Camron D
CD
Evans
Christopher J
CJ
Eitan
Shoshana
S
D000607:Aminoacetonitrile / Q000031:analogs & derivatives / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000037:antagonists & inhibitors; D009270:Naloxone / Q000494:pharmacology; D020665:Septum of Brain / Q000187:drug effects / Q000201:enzymology*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
C424127:SL 327; D009270:Naloxone; D000607:Aminoacetonitrile; D009020:Morphine; D048049:Extracellular Signal-Regulated MAP Kinases