Modulation of the discriminative stimulus effects of mu opioid agonists in rats: II. Effects of dopamine D2/3 agonists.
Dopamine (DA) D2/3 receptor agonists have been shown to attenuate the behavioral effects of mu opioid agonists. This study was designed to examine the modulatory actions of the D2/3 agonists quinelorane, quinpirole and (+/-)-2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (7-OH-DPAT) on the discriminative stimulus effects of the higher-efficacy mu agonists heroin, methadone and morphine, as well as the lower-efficacy agonist nalbuphine, in rats trained to discriminate heroin from water. All three D2/3 agonists attenuated the heroin-like discriminative stimulus effects of morphine, methadone and nalbuphine, whereas quinpirole and 7-OH-DPAT, but not quinelorane, effectively attenuated the discriminative stimulus effects of heroin. Each D2/3 agonist administered alone occasioned water-appropriate responding and decreased rates of responding. These results extend previous findings, which demonstrated that activation of D2/3 receptors attenuates the antinociceptive effects of mu agonists, to now include their discriminative stimulus effects as well. The exact nature of this modulation of opioid effects by dopamine agonists is unclear, and may include neurochemical interactions as well as psychological mechanisms such as perceptual masking.
Cook
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CD
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia 23298-0613, USA. ccook@hsc.vcu.edu
Beardsley
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PM
D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D003932:Heroin / Q000494:pharmacology; D008297:Male; D008691:Methadone / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009042:Motivation; D009266:Nalbuphine / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D011804:Quinolines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D017450:Receptors, Opioid, mu; D013764:Tetrahydronaphthalenes; D019257:Quinpirole; D003932:Heroin; D009020:Morphine; D009266:Nalbuphine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D008691:Methadone; C047726:quinelorane