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-administere d Male Wistar rats were allowed to self-administer cocaine, heroin or salin e for 6 h for 5 consecutive days. Immediately following the last self-admin istration session ('acute drug on board' state), and just before the next s cheduled session ('drug expecting' state), the animals were decapitated and the levels of dynorphin A and B, [Met(5)]- and [Leu(5)]-enkephalin and sub stance P were measured in different brain areas. During the 'acute drug on board' state, peptide levels in animals that self-administered heroin or co caine were not significantly changed. In contrast, during the 'drug expecti ng' state, heroin-treated animals had increased levels of dynorphin A, dyno rphin B and [Met(5)]-enkephalin in the caudal striatum as compared to the c ocaine- and saline-treated animals, and the level of [Leu(5)]-enkephalin wa s increased as compared to the cocaine-treated group. In the septum, an inc rease of [Met(5)]-enkephalin and substance P was observed in the animals ex pecting heroin as compared to the saline- and/or cocaine-treated animals. I n the caudal striatum, substance P levels were elevated in the heroin- and cocaine-expecting animals. In conclusion, heroin, as compared to cocaine, a ppears to have a more pronounced effect on dynorphin, enkephalin and substa nce P levels in the caudal striatum and septum, especially during periods w hen self-administration of the drug is expected. (C) 1999 Elsevier Science B.V. All rights reserved.