Modulation of the discriminative stimulus effects of mu opioid agonists in rats: I. Effects of dopamine D2/3 antagonists. 2004

C D Cook, and P M Beardsley
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia 23298-0613, USA. ccook@hsc.vcu.edu

Mu opioid receptor agonists such as morphine stimulate the release of dopamine (DA) in various brain regions. These increases in DA are thought to be involved in some of the behavioral effects of mu agonists. The present study was designed to examine the modulatory actions of two D2/3 antagonists (nafadotride and eticlopride), the D2/3 partial agonist BP897, the D1/2 antagonist flupenthixol, and the D1 antagonist SCH23390 on the discriminative stimulus effects of the mu partial agonist nalbuphine and the higher-efficacy mu agonists heroin, methadone and morphine, in rats trained to discriminate heroin from water. Both nafadotride and eticlopride attenuated the effects of the mu agonists, whereas BP897 was effective against nalbuphine and partially effective against morphine. Flupenthixol attenuated the heroin-like discriminative stimulus effects of heroin and morphine, although not as completely as nafadotride or eticlopride. SCH23390 was least effective and produced little attenuation. These results demonstrate that the discriminative stimulus effects of mu agonists in rats are more readily attenuated by drugs that block D2-like, rather than D1-like, receptors.

UI MeSH Term Description Entries
D008691 Methadone A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of MORPHINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3) Amidone,Biodone,Dolophine,Metadol,Metasedin,Methaddict,Methadone Hydrochloride,Methadose,Methex,Phenadone,Phymet,Physeptone,Pinadone,Symoron,Hydrochloride, Methadone
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009042 Motivation Those factors which cause an organism to behave or act in either a goal-seeking or satisfying manner. They may be influenced by physiological drives or by external stimuli. Incentives,Disincentives,Expectations,Disincentive,Expectation,Incentive,Motivations
D009266 Nalbuphine A narcotic used as a pain medication. It appears to be an agonist at KAPPA RECEPTORS and an antagonist or partial agonist at MU RECEPTORS. EN-2234A,Nalbuphine Hydrochloride,Nalbuphine Serb,Nubain,EN 2234A,EN2234A
D009281 Naphthalenes Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D011759 Pyrrolidines Compounds also known as tetrahydropyridines with general molecular formula (CH2)4NH. Tetrahydropyridine,Tetrahydropyridines
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D003932 Heroin A narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of Federal Regulations, Title 21 Parts 329.1, 1308.11 (1987). Sale is forbidden in the United States by Federal statute. (Merck Index, 11th ed) Diacetylmorphine,Diamorphine,Diacetylmorphine Hydrochloride,Diagesil,Diamorf,Heroin Hydrochloride,Min-I-Jet Morphine Sulphate,Hydrochloride, Diacetylmorphine,Hydrochloride, Heroin,Min I Jet Morphine Sulphate
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine

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