Discriminative-stimulus effects of morphine in combination with alpha- and beta-noradrenergic agonists and antagonists in rats. 1996

C E Hughes, and T Habash, and L A Dykstra, and M J Picker
Department of Psychology, University of North Carolina, Chapel Hill 27599-3270, USA. chughes@gibbs.oit.unc.edu

Studies have shown that the noradrenergic system is involved in the analgesic effects of opioids and in the expression and development of physical signs of opioid withdrawal. The purpose of the present experiment was to determine if the noradrenergic system was involved in the discriminative effects of morphine in rats trained to discriminate 5.6 mg/kg morphine from saline under a fixed-ratio schedule of food presentation. A range of doses of morphine (0.3-10.0 mg/kg) produced dose-dependent increases in morphine-appropriate responding without substantial decreases in response rate. Several experiments were conducted to determine whether a number of noradrenergic agonists and antagonists 1) substitute for morphine or 2) alter the discriminative-stimulus effects of morphine when administered concurrently. The alpha 2 agonist clonidine (0.003-0.1 mg/kg), the alpha 1 antagonist prazosin (0.1-10.0 mg/kg), the alpha 2 antagonist yohimbine (0.1-10.0 mg/kg), the beta 2 agonist salbutamol (0.03-10.0 mg/kg), and the beta antagonist propranolol (1.0-10.0 mg/kg), neither substituted for morphine nor altered the discriminative-stimulus effects of morphine when administered in combination. These data suggest that the noradrenergic system is not involved in the discriminative-stimulus effects of 5.6 mg/kg morphine in rats.

UI MeSH Term Description Entries
D008297 Male Males
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
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
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D004192 Discrimination, Psychological Differential response to different stimuli. Discrimination, Psychology,Psychological Discrimination
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D058646 Adrenergic alpha-1 Receptor Agonists Compounds that bind to and activate ADRENERGIC ALPHA-1 RECEPTORS. Adrenergic alpha-1 Agonists,Adrenergic alpha-1 Receptor Agonist,Adrenergic alpha1-Agonists,Adrenergic alpha 1 Agonists,Adrenergic alpha 1 Receptor Agonist,Adrenergic alpha 1 Receptor Agonists,Adrenergic alpha1 Agonists,Agonists, Adrenergic alpha-1,alpha1-Agonists, Adrenergic
D058647 Adrenergic alpha-2 Receptor Agonists Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS. Adrenergic alpha-2 Agonists,Adrenergic alpha-2 Receptor Agonist,Adrenergic alpha2-Agonists,Adrenergic alpha 2 Agonists,Adrenergic alpha 2 Receptor Agonist,Adrenergic alpha 2 Receptor Agonists,Adrenergic alpha2 Agonists,Agonists, Adrenergic alpha-2,alpha-2 Agonists, Adrenergic,alpha2-Agonists, Adrenergic

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