Self-administration of dynorphin-[1-13] and D-ala2-dynorphin-[1-11] (kappa opioid agonists) in morphine (mu opioid agonist)-dependent rats. 1983

N Khazan, and G A Young, and D Calligaro

Adult female Sprague-Dawley rats were prepared with permanent cortical EEG and temporalis EMG electrodes and i.v. cannulae. They were made tolerant to and physically dependent on morphine by automatic, hourly injections. These physically dependent rats were then trained to lever press for 10 mg/kg injections of morphine on a fixed ratio (FR) schedule of reinforcement. Upon stabilization of morphine self-administration at a FR-10, dynorphin-[1-13] (DYN) or D-ala2-dynorphin-[1-11] (D-ala2-DYN) at doses of 125 or 250 micrograms/kg/inj was substituted for morphine. Rats self-administered these opioid-like peptides at both dose levels. As expected, self-injections were more numerous at the lower dose. No signs of morphine withdrawal were seen during the peptide substitutions. Following DYN or D-ala2-DYN abstinence, no withdrawal symptoms were noted. The question is raised as to whether DYN or D-ala2-DYN and morphine are producing their reinforcing effects in sustaining self-administration via the same receptor populations. Since morphine abstinence is associated with severe withdrawal symptoms and the peptides studied are not, the involvement of separate receptor populations in the process of dependence on morphine and these opioid-like peptides is indicated. In conclusion, both a mu and two kappa agonists exhibited an analogous reinforcing property in the rat. However, the degree of physical dependence and the intensity of withdrawal differed; being higher with the mu agonist and lower with the kappa agonists.

UI MeSH Term Description Entries
D009021 Morphine Dependence Strong dependence, both physiological and emotional, upon morphine. Morphine Abuse,Morphine Addiction,Abuse, Morphine,Addiction, Morphine,Dependence, Morphine
D009294 Narcotics Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS. Analgesics, Narcotic,Narcotic Analgesics,Narcotic,Narcotic Effect,Narcotic Effects,Effect, Narcotic,Effects, Narcotic
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011957 Receptors, Opioid Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known. Endorphin Receptors,Enkephalin Receptors,Narcotic Receptors,Opioid Receptors,Receptors, Endorphin,Receptors, Enkephalin,Receptors, Narcotic,Receptors, Opiate,Endorphin Receptor,Enkephalin Receptor,Normorphine Receptors,Opiate Receptor,Opiate Receptors,Opioid Receptor,Receptors, Normorphine,Receptors, beta-Endorphin,beta-Endorphin Receptor,Receptor, Endorphin,Receptor, Enkephalin,Receptor, Opiate,Receptor, Opioid,Receptor, beta-Endorphin,Receptors, beta Endorphin,beta Endorphin Receptor,beta-Endorphin Receptors
D004399 Dynorphins A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters. Dynorphin,Dynorphin (1-17),Dynorphin A,Dynorphin A (1-17)
D004569 Electroencephalography Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. EEG,Electroencephalogram,Electroencephalograms
D004723 Endorphins One of the three major groups of endogenous opioid peptides. They are large peptides derived from the PRO-OPIOMELANOCORTIN precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; OPIOID PEPTIDES is used for the broader group. Endorphin
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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