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The discriminative properties of the D1 dopamine agonist dihydrexidine in the rat

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Abstract

The objective of this study was to train rats to discriminate the interoceptive stimuli produced by a selective dopamine D1 agonist. Fourteen male Sprague-Dawley rats acquired the discrimination of the fully effective, high potency, D1 agonist dihydrexidine (DHX) within 20 sessions using a training dose of 3.0 mg/kg. DHX (0.75–4.5 mg/kg) dose-dependently increased DHX-appropriate responding with an ED50=1.44 mg/kg. The selective D1 agonist SKF 38398 (2.0–8.0 mg/kg) dose-responsively generalized with an ED50=3.54 mg/kg; significantly less potent than DHX. The selective D1 antagonist SCH 23390 (0.06–0.12 mg/kg) dose-responsively decreased DHX-appropriate discriminative performance. These data would indicate that DHX is a selective D1 agonist that may allow for testing of the selectivity of other putative D1 agonists in this experimental procedure. Administration of non-selective dopaminergically active drugs, including apomorphine, amphetamine and cocaine, were each shown to produce intermediate DHX-appropriate discriminative performance.

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References

  • Baker LE, Riddle EE, Saunders RB, Appel JB (1993) The role of monoamine uptake in the discriminative effects of cocaine and related compounds. Behav Pharmacol 4:69–79

    Google Scholar 

  • Brewster WK, Nichols DE, Riggs RM, Mottola DM, Lovenberg TW, Lewis MH, Mailman RB (1990) Trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine: a highly potent selective dopamine D1 full agonist. J Med Chem 33:1756–1764

    Google Scholar 

  • Cook LL, Mottola DM, Pettito JM, Lewis MH, Mailman RB (1991) Functional interactions of striatal D1 and D2 dopamine receptors: effects of tissue preparation and lesions. Soc Neurosci Abstr 17:606

    Google Scholar 

  • Cory-Slechta DA, Widzowski DV, Newland MC (1989) Behavioral differentiation of the stimulus properties of a dopaminergic D1 agonist from a D2 agonist. J Pharmacol Exp Ther 250:800–808

    Google Scholar 

  • Cunningham KA, Callahan PM, Appel JB (1985) Dopamine D1 receptor mediation of the discriminative stimulus properties of SKF 38393. Eur J Pharmacol 119:121–125

    Google Scholar 

  • Daly SA, Waddington JL (1993) Behavioural evidence for “D-1-like” dopamine receptor subtypes in rat brain using the new isochroman agonist A 68930 and isoquinoline antagonist BW 737C. Psychopharmacology 113:45–50

    Google Scholar 

  • Darney KJ, Lewis MH, Brewster WK, Nichols DE, Mailman RB (1991) Behavioral effects in the rat of dihydrexidine, a high-potency, full-efficacy D1dopamine receptor agonist. Neuropsychopharmacology 3:187–195

    Google Scholar 

  • Furmidge L, Exner M, Clark D (1991) Role of dopamine D1 and D2 receptors in mediating thed-amphetamine discrimination cue. Eur J Pharmacol 102:191–199

    Google Scholar 

  • Izenwasser S, Katz JL (1993) Differential efficacies of dopamine D1 receptor agonists for stimulating adenylyl cyclase in squirrel monkey and rat. Eur J Pharmacol 246:39–44

    Google Scholar 

  • Kamien JB, Woolverton WL (1985) The D1 dopamine agonist SKF 38393 functions as a discriminative stimulus in rats. Psychopharmacology 87:368–370

    Google Scholar 

  • Kamien JB, Goldberg LI, Woolverton WL (1987) Discriminative stimulus properties of D1 and D2 dopamine agonists in rats. J Pharmacol Exp Ther 242:804–811

    Google Scholar 

  • Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277:93–96

    Google Scholar 

  • Lane JD, Pickering CL, Hooper ML, Fagan K, Tyers MB, Emmett-Oglesby MW (1992) Failure of ondansetron to block the discriminative or reinforcing stimulus effects of cocaine in the rat. Drug Alcohol Depend 30:151–162

    Google Scholar 

  • Levine RR (1983) Pharmacology: drug actions and reactions, 2nd edition. Little-Brown, Boston, pp 181–182

    Google Scholar 

  • Litchfield JT, Wilcoxon F (1949) A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 96:99–113

    Google Scholar 

  • Lovenberg TW, Brewster WK, Mottola DM, Lee RC, Riggs RM, Nichols DE, Lewis MH, Mailman RB (1989) Dihydrexidine, a novel selective high potency full dopamine D-1 receptor agonist. Eur J Pharmacol 166:111–113

    Google Scholar 

  • Melia KF, Spealman RD (1991) Pharmacological characterization of the discriminative-stimulus effects of GBR 12909. J Pharmacol Exp Ther 258:626–632

    Google Scholar 

  • Mottola DM, Brewster WK, Cook LL, Nichols DE, Mailman RB (1992) Dihydrexidine, a novel full efficacy D1 dopamine receptor agonist. J Pharmacol Exp Ther 262:383–393

    Google Scholar 

  • O'Dowd BJ (1993) Structures of dopamine receptors. J Neurochem 60:804–811

    Google Scholar 

  • Rosenzweig-Lipson S, Bergman J, (1993a) Dopamine D1receptor involvement in a discriminative-stimulus effect of SKF 81297 in squirrel monkeys. J Pharmacol Exp Ther 267:765–775

    Google Scholar 

  • Rosenzweig-Lipson S, Bergman J (1993b) Discriminative stimulus effects of cocaine and the high-efficacy D1 agonist SKF 81297 in squirrel monkeys. NIDA Res Monogr 132:253

    Google Scholar 

  • Schechter MD, Greer NL (1987) Evidence that the stimulus properties of apomorphine are mediated by both D1 and D2 receptor activation. Life Sci 40:2461–2471

    Google Scholar 

  • Spealman RD, Bergman J, Madras BK, Melia KF (1991) Discriminative stimulus effects of cocaine in squirrel monkeys: involvement of dopamine receptor subtypes. J Pharmacol Exp Ther 258:945–953

    Google Scholar 

  • Stoof JC, Kebabian JW (1984) Two dopamine receptors: biochemistry, physiology and pharmacology. Life Sc. 35:2281–2296

    Google Scholar 

  • Tallarida RJ, Murray RB (1987) Manual of pharmacologic calculation with computer programs, 2nd edition. Springer, New York

    Google Scholar 

  • Tang AH, Franklin SR (1987) Discriminative stimulus effects of a low dose of apomorphine in the rat. Psychopharmacology 91:61–66

    Google Scholar 

  • Waddington JL, O'Boyle KM (1989) Drugs acting on brain dopamine receptors: a conceptual re-evaluation five years after the first selective D-1 antagonist. Pharmacol Ther 43:1–59/+R

    Google Scholar 

  • Walker OD, Black DM, Eckerman DA, Nichols DE, Mailman RB (1993) Behavioral and pharmacological determinants of D1 dopamine agonist substitution for the discriminative stimulus properties induced by dihydrexidine. Soc Neurosci Abstr 19:1829

    Google Scholar 

  • Watts VJ, Lawler CP, Gilmore JH, Sutherland SB, Nichols DE, Mailman RB (1993) Dopamine D1 receptors: efficacy of full (dihydrexidine) versus partial (SKF 38393) agonists in primates versus rodents. Eur J Pharmacol 242:165–172

    Google Scholar 

  • Weathersby RT, Appel, JB (1986) Dopamine D2receptor mediation of the discriminative stimulus properties of LY 171555 (quinpirole) Eur J Pharmacol 132:87–91

    Google Scholar 

  • Williams JEG, Sutherland JV, Woolverton WL (1990) Evaluation of the interaction between D1 and D2 receptors in a drug discrimination paradigm. Behav Neural Biol 53:378–392

    Google Scholar 

  • Woolverton WL, Kamien JB, Goldberg LI (1985) Effects of selective dopamine (DA) receptor agonists in rats trained to discriminate apomorphine from saline. Pharmacol Biochem Behav 22:577–581

    Google Scholar 

  • Woolverton WL, Kamien JB, Goldberg LI (1987) Pharmacological analysis of the apomorphine discriminative stimulus in rhesus monkeys. J Pharmacol Exp Ther 241:213–217

    Google Scholar 

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  1. Department of Pharmacology, Northeastern Ohio Universities College of Medicine, 44272, Rootstown, OH, USA

    M. D. Schechter

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  1. M. D. Schechter
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Schechter, M.D. The discriminative properties of the D1 dopamine agonist dihydrexidine in the rat. Psychopharmacology 119, 79–84 (1995). https://doi.org/10.1007/BF02246057

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  • DOI: https://doi.org/10.1007/BF02246057

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