A heroin-, but not a cocaine-expecting, self-administration state preferentially alters endogenous brain peptides.
The purpose of the current study was to assess neuropeptidergic alterations during a phase of the drug addiction cycle associated with drug craving as compared to a time period when the drug had been recently self-administered. Male Wistar rats were allowed to self-administer cocaine, heroin or saline for 6 h for 5 consecutive days. Immediately following the last self-administration session ('acute drug on board' state), and just before the next scheduled session ('drug expecting' state), the animals were decapitated and the levels of dynorphin A and B, [Met5]- and [Leu5]-enkephalin and substance P were measured in different brain areas. During the 'acute drug on board' state, peptide levels in animals that self-administered heroin or cocaine were not significantly changed. In contrast, during the 'drug expecting' state, heroin-treated animals had increased levels of dynorphin A, dynorphin B and [Met5]-enkephalin in the caudal striatum as compared to the cocaine- and saline-treated animals, and the level of [Leu5]-enkephalin was increased as compared to the cocaine-treated group. In the septum, an increase of [Met5]-enkephalin and substance P was observed in the animals expecting heroin as compared to the saline- and/or cocaine-treated animals. In the caudal striatum, substance P levels were elevated in the heroin- and cocaine-expecting animals. In conclusion, heroin, as compared to cocaine, appears to have a more pronounced effect on dynorphin, enkephalin and substance P levels in the caudal striatum and septum, especially during periods when self-administration of the drug is expected.
Cappendijk
S L
SL
Karolinska Institute, Department of Clinical Neurosciences, Stockholm, Sweden. engelen@cs.fsu.edu
Hurd
Y L
YL
Nylander
I
I
van Ree
J M
JM
Terenius
L
L
D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology*; D004399:Dynorphins / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D003932:Heroin / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D009479:Neuropeptides / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013373:Substance P / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000378:metabolism*; D013997:Time Factors