c-Fos and peptide immunoreactivities in the central extended amygdala of morphine-dependent rats after naloxone-precipitated withdrawal.
The central extended amygdala, a forebrain macrostructure, may represent a common substrate for acute drug reward and the dysphoric effects of drug withdrawal. To test its involvement during opiate withdrawal, we studied the distribution of c-Fos immunoreactive neurons, in relation to their neuropeptide content, in brain sections from morphine-dependent or naive rats, killed 90 min after naloxone or saline intraperitoneal injection. Naloxone treatment in naive rats induced a slight increase in c-Fos immunoreactivity in the central amygdaloid nucleus, the lateral bed nucleus of the stria terminalis and the interstitial nucleus of the posterior limb of the anterior commissure. In morphine-dependent rats, naloxone injection significantly increased the number of c-Fos-positive neurons in these structures as well as in the majority of the other central extended amygdala components. Double immunocytochemistry was used to determine the neurochemical nature of c-Fos-positive neurons in the central extended amygdala. Corticotropin-releasing factor- and methionine-enkephakin-immunoreactive neurons displayed c-Fos immunoreactivity in naive rats after naloxone injection, whereas only enkephalinergic neurons were found to be c-Fos positive in morphine-dependent rats after naloxone injection. The possible involvement of the corticotropin-releasing factor system during withdrawal is discussed. These results suggest that the whole central extended amygdala is activated during opiate withdrawal, with a lateral to medial decreasing gradient, and emphasize the role of peptidergic systems in this morphofunctional continuum.
Veinante
Pierre
P
UMR 7519, CNRS/Université Louis Pasteur, 21 rue René Descartes, 67084 Strasbourg, France. veinantep@neurochem.u-strasbg.fr
Stoeckel
Marie-Elisabeth
ME
Lasbennes
François
F
Freund-Mercier
Marie-José
MJ
D000679:Amygdala / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D003078:Colchicine / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000378:metabolism; D006074:Gout Suppressants / Q000494:pharmacology; D008297:Male; D009021:Morphine Dependence / Q000188:drug therapy / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D009474:Neurons / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D006074:Gout Suppressants; D009292:Narcotic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D009270:Naloxone; D004744:Enkephalin, Methionine; D003346:Corticotropin-Releasing Hormone; D003078:Colchicine