Elevated basal firing rates and enhanced responses to 8-Br-cAMP in locus coeruleus neurons in brain slices from opiate-dependent rats.
Extracellular, single unit activity was recorded in noradrenergic neurons of the nucleus locus coeruleus (LC) in brain slices prepared from rats treated chronically with morphine. In contrast to previous reports, basal firing rates of LC neurons were 2-fold higher in slices from opiate-dependent animals compared to controls and they remained elevated for at least 7 h. In neurons from dependent animals the maximal excitation in response to 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP), but not the EC50, was found to be substantially greater than in controls. This result parallels biochemical evidence of an up-regulation of the cAMP pathway in the LC of opiate-dependent animals. There was no difference in the response to glutamate between cells from dependent and control animals. We conclude that an increase in basal firing rate, possibly mediated by an up-regulation of the intrinsic cAMP pathway, contributes to the hyperactivity of the LC during opiate withdrawal in vivo.
Kogan
J H
JH
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT.
Nestler
E J
EJ
Aghajanian
G K
GK
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000187:drug effects*; D008297:Male; D008839:Microelectrodes; D009271:Naltrexone / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains
D015124:8-Bromo Cyclic Adenosine Monophosphate; D009271:Naltrexone