Skip to main content
SpringerLink
Log in

Relationship between D 1 dopamine receptors, adenylate cyclase, and the electrophysiological responses of rat nucleus accumbens neurons

  • Full Papers
  • Published:
Journal of Neural Transmission / General Section JNT Aims and scope Submit manuscript

Summary

The electrophysiological effects of three selective D 1 dopamine (DA) receptor agonists, which exhibit different potencies and efficacies for stimulation of adenylate cyclase, were compared in the rat nucleus accumbens (NAc) using single unit recording and microiontophoretic techniques. The partial agonists SKF 75670 and SKF 38393, and the full agonist SKF 81297 produced nearly identical current-response curves for the inhibition of firing of NAc neurons. In rats acutely depleted of DA byα-methyl-p-tyrosine (AMPT) pretreatment, all three D 1 agonists enabled the inhibition of firing produced by the selective D 2 receptor agonist quinpirole, with SKF 38393 exerting the greatest efficacy, followed by SKF 81297 and SKF 75670. Thus, no apparent relationship was found between the previously reported ability of these compounds to stimulate cyclic adenosine monophosphate (cAMP) production and their ability either to inhibit the firing of NAc neurons or to enable quinpirole-mediated inhibition of firing in DA-depleted rats. In addition, the membrane-permeable cAMP analog 8-bromo-cAMP also caused a current-dependent inhibition of the firing of NAc neurons, but failed to enable quinpirole-mediated inhibition in AMPT-pretreated animals. These results suggest either that only a small percentage of D 1 receptors need to be stimulated to produce these electrophysiological effects, or that D 1 receptors exist within the rat NAc which are linked to transduction mechanisms other than, or in addition to, adenylate cyclase.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Andersen PH, Braestrup C (1986) Evidence for different states of the dopamine D 1 receptor: clozapine and fluperlapine may preferentially label an adenylate cyclase-coupled state of the D 1 receptor. J Neurochem 47: 1822–1831

    PubMed  Google Scholar 

  • Andersen PH, Jansen JA (1990) Dopamine receptor agonists: selectivity and dopamine D1 receptor efficacy. Eur J Pharmacol -Mol Pharmacol Sect 188: 335–347

    Google Scholar 

  • Andersen PH, Gingrich JA, Bates MD, Dearry A, Falardeau P, Senogles SE, Caron MG (1990) Dopamine receptor subtypes: beyond the D1/D2 classification. Trends Pharmacol Sci 11: 231–236

    PubMed  Google Scholar 

  • Andersen PH, Nielsen EB, Scheel-Kruger J, Jansen JA, Hohlweg R (1987) Thienopyridine derivatives identified as the first selective, full efficacy, dopamine D 1 receptor agonists. Eur J Pharmacol 137: 291–292

    PubMed  Google Scholar 

  • Arnt J (1985) Behavioral stimulation is induced by separate dopamine D-1 and D-2 receptor sites in reserpine-pretreated but not in normal rats. Eur J Pharmacol 113: 79–88

    PubMed  Google Scholar 

  • Arnt J (1988) The discriminative stimulus properties of the D-1 agonist SKF 38393 and the D-2 agonist (−)-NPA are mediated by separate mechanisms. Life Sci 42: 565–574

    PubMed  Google Scholar 

  • Arnt J, Perregaard J (1987) Synergistic interaction between dopamine D-1 and D-2 receptor agonists: circling behavior of rats with hemitransection. Eur J Pharmacol 143: 45–53

    PubMed  Google Scholar 

  • Arnt J, Hyttel J, Perregaard J (1987) Dopamine D-1 receptor agonists combined with the selective D-2 agonist quinpirole facilitate the expression of oral stereotyped behaviour in rats. Eur J Pharmacol 133: 137–145

    PubMed  Google Scholar 

  • Arnt J, Bogeso KP, Hyttel J (1988) Dopamine D-1 and D-2 receptor differentiation revealed by behavioural studies in rats. In: Beart PM, Woodruff GN, Jackson DM (eds) Phar-macology and functional regulation of dopaminergic neurons. PSG Publishing, Littleton, MA, pp 110–116

    Google Scholar 

  • Barone P, Davis TA, Braun AR, Chase TN (1986) Dopaminergic mechanisms and motor function: characterization of D-1 and D-2 dopamine receptor interactions. Eur J Pharmacol 123: 109–114

    PubMed  Google Scholar 

  • Barnett JV, Kuczenski R (1986) Desensitization of rat striatal dopamine-stimulated aden-ylate cyclase after acute amphetamine administration. J Pharmacol Exp Ther 237: 820–825

    PubMed  Google Scholar 

  • Barton AC, Sibley DR (1990) Agonist-induced desensitization of D1-dopamine receptors linked to adenylyl cyclase activity in cultured NS20Y neuroblastoma cells. Mol Pharmacol 38: 531–541

    PubMed  Google Scholar 

  • Battaglia G, Norman AB, Hess EJ, Creese I (1986) Functional recovery of D 1 dopamine receptor-mediated stimulation of rat striatal adenylate cyclase activity following irre-versible receptor modification by N-Ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ): evidence for spare receptors. Neurosci Lett 69: 290–295

    PubMed  Google Scholar 

  • Bickford-Winer P, Kim M, Boyajian C, Cooper DMF, Freedman R (1990) Effects of pertussis toxin on caudate neuron electrophysiology: studies with dopamine D1 and D2 agonists. Brain Res 533: 263–267

    PubMed  Google Scholar 

  • Bloom FE (1974) To spritz or not to spritz: the doubtful value of aimless iontophoresis. Life Sci 14: 1819–1834

    PubMed  Google Scholar 

  • Braun AR, Chase TN (1986) Obligatory D 1-D 2 receptor coactivation and the generation of dopamine agonist related behaviors. Eur J Pharmacol 131: 301–306

    PubMed  Google Scholar 

  • Breese GR, Meuller RA (1985) SCH 23390 antagonism of a D-2 agonist depends upon catecholaminergic neurons. Eur J Pharmacol 113: 109–114

    PubMed  Google Scholar 

  • Cameron DL, Crocker AD (1988) Alkylation of striatal dopamine receptors abolishes stereotyped behavior but has no effect on dopamine stimulated adenylate cyclase activity. Neurosci Lett 90: 165–171

    PubMed  Google Scholar 

  • Carlson JH, Bergstrom DA, Walters JR (1987) Stimulation of both D 1 and D 2 dopamine receptors appears necessary for full expression of postsynaptic effects of dopamine agonists: a neurophysiological study. Brain Res 400: 205–218

    PubMed  Google Scholar 

  • Chneiweiss H, Glowinski J, Premont J (1990) Dopamine-induced homologous and het-erologous desensitizations of adenylate cyclase-coupled receptors on striatal neurons. Eur J Pharmacol-Mol Pharmacol Sect 189: 287–292

    Google Scholar 

  • Clark D, White FJ (1987) Review: D 1 dopamine receptor —The search for a function: a critical evaluation of the D 1/D 2 dopamine receptor classification and its functional implications. Synapse 1: 347–388

    PubMed  Google Scholar 

  • Dearry A, Gingrich JA, Falardeau P, Fremeau Jr RT, Bates MD, Caron MG (1990) Molecular cloning and expression of the gene for a human D1 dopamine receptor. Nature 347: 72–76

    PubMed  Google Scholar 

  • De Keyser J, Dierckx R, Vanderheyden P, Ebinger G, Vauquelin G (1988) D1 dopamine receptors in human putamen, frontal cortex and calf retina: differences in guanine nucleotide regulation of agonist binding and adenylate cyclase stimulation. Brain Res 443: 77–84

    PubMed  Google Scholar 

  • De Keyser J, Walraevens H, Ebinger G, Vauquelin G (1989) In human brain two subtypes of D 1 dopamine receptors can be distinguished on the basis of differences in guanine nucleotide effect on agonist binding. J Neurochem 53: 1096–1102

    PubMed  Google Scholar 

  • Felder CC, Blecher M, Jose PA (1989 a) Dopamine-1-mediated stimulation of phospholipase C activity in rat renal cortical membranes. J Biol Chem 264: 8739–8745

    PubMed  Google Scholar 

  • Felder CC, Jose PA, Axelrod J (1989 b) The dopamine-1 agonist, SKF 82526, stimulates phospholipase C activity independent of adenylate cyclase. J Pharmacol Exp Ther 248: 171–175

    PubMed  Google Scholar 

  • Henry DJ, Greene MA, White FJ (1989) Electrophysiological effects of cocaine in the mesoaccumbens dopamine system: repeated administration. J Pharmacol Exp Ther 251: 833–839

    PubMed  Google Scholar 

  • Hess EJ, Battaglia G, Norman AB, Creese I (1987) Differential modification of striatal D 1 dopamine receptors and effector moieties by N-ethoxycarbonyl-2-ethoxy-1,2-dih-ydroquinoline in vivo and in vitro. Mol Pharmacol 31: 50–57

    PubMed  Google Scholar 

  • Hicks TP (1984) The history and development of microiontophoresis in experimental neu-robiology. Prog Neurobiol 22: 185–240

    PubMed  Google Scholar 

  • Hu X-T, Wang RY (1988) Comparison of effects of D-1 and D-2 receptor agonists on neurons in the rat caudate-putamen: an electrophysiological study. J Neurosci 8: 4340–4348

    PubMed  Google Scholar 

  • Hu X-T, Wachtel SR, Galloway MP, White FJ (1990) Lesions of the nigrostriatal dopamine projection increase the inhibitory effects of D1 and D2 dopamine agonists on caudate-putamen neurons and relieve D2 receptors from the necessity of D1 receptor stimulation. J Neurosci 10: 2318–2329

    PubMed  Google Scholar 

  • Jackson DM, Hashizume M (1986) Bromocriptine induces marked locomotor stimulation in dopamine-depleted mice when D-1 dopamine receptors are stimulated with SKF 38393. Psychopharmacology 90: 147–149

    PubMed  Google Scholar 

  • Jiang LH, Kasser RJ, Altar CA, Wang RY (1990) One year of continuous treatment with haloperidol or clozapine fails to induce a hypersensitive response of caudate putamen neurons to dopamine D 1 and D 2 receptor agonists. J Pharmacol Exp Ther 253: 1198–1205

    PubMed  Google Scholar 

  • Johansen PA, Clark D, White FJ (1988) B-HT 920 stimulates postsynaptic D 2 dopamine receptors in the normal rat: electrophysiological and behavioral evidence. Life Sci 43: 515–524

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Kelly E, Batty I, Nahorski SR (1988) Dopamine receptor stimulation does not affect phosphoinositide hydrolysis in slices of rat striatum. J Neurochem 51: 918–924

    PubMed  Google Scholar 

  • Kilts CD, Anderson CM, Ely TD, Mailman RB (1988) The biochemistry and pharmacology of mesoamygdaloid dopamine neurons. In: Kalivas PW, Nemeroff CB (eds) The me-socortical dopamine system. Ann NY Acad Sci 537: 173–187

  • Longoni R, Spina L, Di Chiara G (1987) Permissive role of D-1 receptor stimulation for the expression of D 2 mediated behavioural responses: a quantitative phenomenological study in rats. Life Sci 41: 2135–2145

    PubMed  Google Scholar 

  • Mahan LC, Burch RM, Monsma Jr FJ, Sibley DR (1990) Expression of striatal D 1 dopamine receptors coupled to inositol phosphate production and Ca2+ mobilization inXenopus oocytes. Proc Natl Acad Sci USA 87: 2196–2200

    PubMed  Google Scholar 

  • Mailman RB, Schulz DW, Kilts CD, Lewis MH, Rollema H, Wyrick S (1986) The mul-tiplicity of the D 1 dopamine receptor. In: Breese GR, Creese I (eds) Neurobiology of central D 1-dopamine receptors. Plenum Press, New York, pp 53–72

    Google Scholar 

  • Meller E, Bordi F, Bohmaker K (1988) Enhancement by the D 1 dopamine agonist SKF 38393 of specific components of stereotypy elicited by the D 2 agonists LY171555 and RU 24213. Life Sci 42: 2561–2567

    PubMed  Google Scholar 

  • Memo M, Hanbauer I (1984) Phosphorylation of membrane proteins in response to per-sistent stimulation of adenylate cyclase linked to dopamine receptors in slices of stria-tum. Neuropharmacology 23: 449–455

    PubMed  Google Scholar 

  • Memo M, Lovenberg W, Hanbauer I (1982) Agonist-induced subsensitivity of adenylate cyclase coupled with a dopamine receptor in slices from rat corpus striatum. Proc Natl Acad Sci USA 79: 4456–4460

    PubMed  Google Scholar 

  • Molloy AG, Waddington JL (1985) The enantiomers of SKF 83566, a new selective D-1 dopamine receptor antagonist, stereospecifically block stereotyped behaviour induced by apomorphine and by the selective D-2 agonist RU 24213. Eur J Pharmacol 116: 183–186

    PubMed  Google Scholar 

  • Monsma Jr FJ, Mahan LC, McVittie LD, Gerfen CR, Sibley DR (1990) Molecular cloning and expression of a D1 dopamine receptor linked to adenylyl cyclase activation. Proc Natl Acad Sci USA 87: 6723–6727

    PubMed  Google Scholar 

  • Murray AM, Waddington JL (1989) The induction of grooming and vacuous chewing by a series of selective D-1 dopamine receptor agonists: two directions of D-1∶D-2 in-teraction. Eur J Pharmacol 160: 377–384

    PubMed  Google Scholar 

  • Nielsen EB, Randrup K, Andersen PH (1989) Amphetamine discrimination: effects of dopamine receptor agonists. Eur J Pharmacol 160: 253–262

    PubMed  Google Scholar 

  • Nisenbaum ES, Orr WB, Berger TW (1988) Evidence for two functionally distinct sub-populations of neurons within the rat striatum. J Neurosci 8: 4138–4150

    PubMed  Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, New York

    Google Scholar 

  • Pizzi M, Da Prada M, Valerio A, Memo M, Spano PF, Haefely WE (1988) Dopamine D 2 receptor stimulation inhibits inositol phosphate generating system in rat striatal slices. Brain Res 456: 235–240

    PubMed  Google Scholar 

  • Pugh MT, O'Boyle KM, Molloy AG, Waddington JL (1985) Effects of the putative D-1 antagonist SCH 23390 on stereotyped behaviour induced by the D-2 agonist RU 24213. Psychopharmacology 87: 308–312

    PubMed  Google Scholar 

  • Roberts-Lewis JM, Roseboom PH, Iwaniec LM, Gnegy ME (1986) Differential downre-gulation of D 1-stimulated adenylate cyclase activity in rat forebrain after in vivo amphetamine treatments. J Neurosci 6: 2245–2251

    PubMed  Google Scholar 

  • Roseboom PH, Gnegy ME (1989) Acute in vivo amphetamine produced a homologous desensitization of dopamine receptor-coupled adenylate cyclase activities and decreased agonist binding to the D 1 site. Mol Pharmacol 34: 148–156

    Google Scholar 

  • Salmoiraghi GC, Weight F (1967) Micromethods in neuropharmacology: an approach to the study of anesthetics. Anesthesiology 28: 54–63

    PubMed  Google Scholar 

  • Schulz DW, Stanford EJ, Wyrick SW, Mailman RB (1985) Binding of [3H]-SCH 23390 in rat brain: regional distribution and effects of assay conditions and GTP suggest interactions at a D 1-like dopamine receptor. J Neurochem 45: 1601–1611

    PubMed  Google Scholar 

  • Siggins GR, Hoffer BJ, Ungerstedt U (1974) Electrophysiological evidence for involvement of cyclic adenosine monophosphate in dopamine responses of caudate neurons. Life Sci 15: 779–792

    PubMed  Google Scholar 

  • Skirboll LR, Bunney BS (1979) The effects of acute and chronic haloperidol treatment on spontaneously firing neurons in the caudate nucleus of the rat. Life Sci 25: 1419–1434

    PubMed  Google Scholar 

  • Sunahara RK, Niznik HB, Weiner DM, Stormann TM, Brann MR, Kennedy JL, Gelernter JE, Rozmahel R, Yang Y, Israel Y, Seeman P, O'Dowd BF (1990) Human dopamine D1 receptor encoded by an intronless gene on chromosome 5. Nature 347: 80–83

    PubMed  Google Scholar 

  • Undie AS, Friedman E (1990) Stimulation of a dopamine D1 receptor enhances inositol phosphates formation in rat brain. J Pharmacol Exp Ther 253: 987–992

    PubMed  Google Scholar 

  • Wachtel SR, Hu X-T, Galloway MP, White FJ (1989) D 1 dopamine receptor stimulation enables the postsynaptic, but not autoreceptor, effects of D 2 dopamine agonists in nigrostriatal and mesoaccumbens dopamine systems. Synapse 4: 327–346

    PubMed  Google Scholar 

  • Waddington JL, O'Boyle KM (1987) The D-1 dopamine receptor and the search for its functional role: from neurochemistry to behavior. Rev Neurosci 1: 157–184

    Google Scholar 

  • Walters JR, Bergstrom DA, Carlson JH, Chase TN, Braun AR (1987) D 1 dopamine receptor activation required for postsynaptic expression of D 2 agonist effects. Science 236: 719–722

    PubMed  Google Scholar 

  • White FJ (1987) D-1 dopamine receptor stimulation enables the inhibition of nucleus accumbens neurons by a D 2 receptor agonist. Eur J Pharmacol 135: 101–105

    PubMed  Google Scholar 

  • White FJ, Bednarz LM, Wachtel SR, Hjorth S, Brooderson RJ (1988) Is stimulation of both D 1 and D 2 receptors necessary for the expression of dopamine-mediated be-haviors? Pharmacol Biochem Behav 30: 189–193

    PubMed  Google Scholar 

  • White FJ, Wachtel SR, Johansen PA, Einhorn LC (1987) Electrophysiological studies of the rat mesoaccumbens dopamine system: focus on dopamine receptor subtypes, in-teractions, and the effects of cocaine. In: Chiodo LC, Freeman AS (eds) Neurophys-iology of dopamine systems —current status and clinical perspectives. Lakeshore, Detroit, pp 317–365

    Google Scholar 

  • White FJ, Wang RY (1986) Electrophysiological evidence for the existence of both D-1 and D-2 dopamine receptors in the rat nucleus accumbens. J Neurosci 6: 274–280

    PubMed  Google Scholar 

  • Woodruff GN, McCarthy PS, Walker RJ (1976) Studies on the pharmacology of neurones in the nucleus accumbens of the rat. Brain Res 115: 233–242

    PubMed  Google Scholar 

  • Zhou Q-Y, Grandy DK, Thambi L, Kushner JA, Van Tol HHM, Cone R, Pribnow D, Salon J, Bunzow JR, Civelli O (1990) Cloning and expression of human and rat D1 dopamine receptors. Nature 347: 76–80

    PubMed  Google Scholar 

Download references

Author information

Author notes

  1. F. J. White

    Present address: Neuropsychopharmacology Laboratory, Lafayette Clinic, Detroit, MI, USA

Authors and Affiliations

  1. Department of Psychiatry, Wayne State University School of Medicine, USA

    P. A. Johansen, X. -T. Hu & F. J. White

  2. Neuropsychopharmacology Laboratory, Lafayette Clinic, Detroit, MI, USA

    P. A. Johansen & X. -T. Hu

Authors
  1. P. A. Johansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. X. -T. Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. J. White
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Johansen, P.A., Hu, X.T. & White, F.J. Relationship between D 1 dopamine receptors, adenylate cyclase, and the electrophysiological responses of rat nucleus accumbens neurons. J. Neural Transmission 86, 97–113 (1991). https://doi.org/10.1007/BF01250571

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01250571

Keywords

Search

Navigation