Yuko Fukunaga and Shiroh Kishioka
Department of Pharmacology, Wakayama Medical College, 811-1 Kimiidera,
Wakayama-City, Wakayama 641-0012, Japan
Abstract: The effects of opioid (e.g., morphine) withdrawal on
levels of endogenous opioid peptides and their mRNA in the various brain
regions have been studied. However, the role of this opioidergic mechanism
in the mediation of opioid withdrawal is not fully understood. Preproenkephalin
(PPE) mRNA in the caudal periaqueductal gray (cPAG), an important brain
region in opioid withdrawal, is increased by both opioid antagonist (naloxone)-precipitated
and spontaneous morphine withdrawal, but not by various other stresses in
rats, indicating a role of endogenous enkephalins in the cPAG in morphine
withdrawal. In addition, PPE mRNA levels in the cPAG increase in the course
of the dissipation of morphine withdrawal, and they are returned to the
control levels after disappearance of morphine withdrawal signs. Local administration
of an enkephalin analog or peptidase inhibitors into the cPAG suppresses
morphine withdrawal signs. These facts suggest that enkephalinergic neurons
in the PAG may have a critical role in the recovery phase of morphine withdrawal.
Recently, an involvement of transcription factors in morphine withdrawal
has been suggested. Thus, the possible role of transcription factors in
the regulation of PPE gene expression in the cPAG during morphine withdrawal
is also discussed.
Keywords: Enkephalin, Preproenkephalin mRNA, Morphine withdrawal, Periaqueductal
gray, Transcription factor