Upregulation of galanin binding sites and GalR1 mRNA levels in the mouse locus coeruleus following chronic morphine treatments and precipitated morphine withdrawal.
The neuropeptide galanin and its receptors are expressed in the locus coeruleus (LC), a brain area associated with drug dependence and withdrawal. Although galanin peptide mRNA levels do not change during withdrawal, it is not known whether galanin receptor levels are regulated following opiate withdrawal. This study demonstrates that galanin binding in the LC is upregulated by chronic-intermittent morphine administration or by precipitated withdrawal, but not by acute morphine treatment, suggesting that increased activity in the LC may be able to regulate galanin binding sites. Moreover, the increase in galanin binding sites seems to be caused by increased transcription or stabilization of the galanin receptor 1 (GalR1) gene, because there is a dramatic increase in mRNA levels following withdrawal in the LC. It is, therefore, possible that the increase in GalR1 could be an adaptive mechanism that leads to regulation of cAMP levels and possibly firing rate of LC neurons.
Zachariou
V
V
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508, USA.
Thome
J
J
Parikh
K
K
Picciotto
M R
MR
D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D019004:Galanin / Q000378:metabolism* / Q000494:pharmacology; D017403:In Situ Hybridization; D007457:Iodine Radioisotopes; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000008:administration & dosage*; D009271:Naltrexone / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide; D009271:Naltrexone; D009020:Morphine; D019004:Galanin