Expression of fos-related antigens in the nucleus accumbens during opiate withdrawal and their attenuation by a D2 dopamine receptor agonist.
Previous studies from this laboratory indicated that D2 dopamine (DA) receptors within the nucleus accumbens (NAc) are important for regulating somatic signs of opiate withdrawal. The present study measured the expression of Fos-related antigens (FRAs) within the NAc during opiate withdrawal to determine whether decreases in somatic withdrawal signs produced by a D2 receptor agonist are accompanied by related changes in accumbens neuronal activity. In an initial experiment, quantitative analyses of FRA immunoreactivity revealed increases in the number of FRA-positive cells throughout the NAc of opiate dependent animals undergoing naltrexone-precipitated withdrawal relative to dependent or non-dependent animals that did not experience withdrawal. A second experiment showed that somatic signs and FRA expression within the NAc could each be attenuated when the D2 agonist propylnorapomorphine (NPA; 0.1 or 0.3 mg/kg, i.p.) was administered prior to naltrexone-precipitated withdrawal. These findings suggest that D2 regulation of neuronal activity within the NAc may be important for the expression of opiate withdrawal symptoms.
Walters
C L
CL
Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Medical Center, Philadelphia, USA.
Aston-Jones
G
G
Druhan
J P
JP
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000009:adverse effects*; D009714:Nucleus Accumbens / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D016760:Proto-Oncogene Proteins c-fos; D017448:Receptors, Dopamine D2; C009074:N-n-propylnorapomorphine; D009271:Naltrexone; D009020:Morphine; D018021:Lithium Chloride; D001058:Apomorphine