Abstract
Dopaminergic mechanisms are believed to play a prominent role in the self-administration of cocaine and other abused stimulants. The contribution of D2 receptors is now well established, but less is known about the role of D1 receptors in the reinforcing effects of these drugs. To help clarify the role of D1 mechanisms in stimulant self-administration, agonists differing in D1 receptor selectivity (SKF 81297>SKF 82958>SKF 77434) and efficacy (SKF 82958>SKF 81297>SKF 77434) were studied for their ability to maintain IV self-administration in squirrel monkeys previously trained to self-administer cocaine. Up to a 100-fold range of doses of each D1 agonist was studied under both a fixed-ratio (FR) and a second-order fixed-interval (FI) schedule of reinforcement. Parallel studies were conducted with the D2 receptor agonists, (+)-PHNO and quinpirole, under the second-order FI schedule. Of the three D1 agonists, only SKF 82958 maintained consistent self-administration under both the FR and second-order FI schedules and had dose-related effects that were qualitatively similar to those of (+)-PHNO and quinpirole under the latter condition. SKF 81297, which has high selectivity at D1 receptors and intermediate agonist efficacy, maintained self-administration in the majority of monkeys under the FR schedule, but did not maintain self-administration under the second-order FI schedule. SKF 77434, which has moderate selectivity at D1 receptors and low agonist efficacy, did not maintain self-administration under either schedule. The results suggest that the ability of D1 agonists to maintain IV self-administration in squirrel monkeys depends both on the type of schedule and on the pharmacological properties (i.e. selectivity and efficacy) of the particular drug. These results are also consistent with the view that D1, in addition to D2, receptor mechanisms play a role in the self-administration of abused stimulants.
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References
Andersen PH, Jansen JA (1990) Dopamine receptor agonists: selectivity and dopamine D1 receptor efficacy. Eur J Pharmacol 188:335–347
Baxter BL, Gluckman MI, Stein L, Scerni RA (1974) Self-injection of apomorphine in the rat: positive reinforcement by a dopamine receptor stimulant. Pharmacol Biochem Behav 2:387–391
Bergman J, Johanson CE (1985) The reinforcing properties of diazepam under several conditions in the rhesus monkey. Psychopharmacology 86:108–113
Bergman J, Spealman RD (1988) Behavioral effects of histamine H1 antagonists: comparison with other drugs and modification by haloperidol. J Pharmacol Exp Ther 245:471–478
Bergman J, Kamien JB, Spealman RD (1990) Antagonism of cocaine self-administration by selective D1 and D2 antagonists. Behav Pharmacol 1:355–363
Bergman J, Rosenzweig-Lipson S, Spealman RD (1995) Differential effects of dopamine D1 and D2 receptor agonists on schedule-controlled behavior of squirrel monkeys. J Pharmacol Exp Ther 273:40–48
Bergman J, Spealman RD, Madras BK, Rosenzweig-Lipson S (1996) Agonist efficacy and the behavioral effects of dopamine D1 receptor ligands: drug interaction studies in squirrel monkeys. J Pharmacol Exp Ther 276:942–950
Briggs CA, Pollock NJ, Frail DE, Paxson CL, Rakowski RD, Kang CH, Kebabian JW (1991) Activation of the 5-HT1c receptor expressed in Xenopus oocytes by the benzazepines SCH 23390 and SKF 38393. Br J Pharmacol 104:1038–1044
Caine SB, Koob GF (1994) Effects of dopamine D1 and D2 antagonists on cocaine self-administration under different schedules of reinforcement in the rat. J Pharmacol Exp Ther 270:209–218
Corrigall WA, Coen KM (1991) Cocaine self-administration is increased by both D1 and D2 dopamine antagonists. Pharmacol Biochem Behav 39:799–802
Gnanalingham KK, Erol DD, Hunter AJ, Smith LA, Jenner P, Marsden CD (1995) Differential anti-Parkinson effects of benzazepine D1 dopamine agonists with varying efficacies in the MPTP-treated common marmoset. Psychopharmacology 117:275–286
Goldberg SR (1973) Comparable behavior maintained under fixed-ratio and second-order schedules of food presentation, cocaine injection ord-amphetamine injection in the squirrel monkey. J Pharmacol Exp Ther 186:18–30
Gonzalez FA, Goldberg SR (1977) Effects of cocaine andd-amphetamine on behavior maintained under various schedules of food presentation in squirrel monkeys. J Pharmacol Exp Ther 201:847–852
Heikkila RD, Orlansky H, Cohen G (1975) Studies on the distinction between uptake inhibition and release of3H-dopamine uptake in rat brain tissue slices. Biochem Pharmacol 24:847–852
Herd JA, Morse WH, Kelleher RT, Jones LG (1969) Arterial hypertension in the squirrel monkey during behavioral experiments. Am J Physiol 217:24–29
Hoffmeister F, Schlichting UU (1972) Reinforcing properties of some opiates and opioids in rhesus monkeys with histories of cocaine and codeine self-administration. Psychopharmacology 23:55–74
Hubner CB, Moreton JE (1991) Effects of selective D1 and D2 dopamine antagonists on cocaine self-administration in the rat. Psychopharmacology 105:151–156
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
Kamien JB, Woolverton WL (1989) A pharmacological analysis of the discriminative stimulus properties ofd-amphetamine in rhesus monkeys. J Pharmacol Exp Ther 248:938–946
Katz JL, Alling K, Shores E, Witkin JM (1995) Effects of D1 dopamine agonists on schedule-controlled behavior in squirrel monkeys. Behav Pharmacol 6:143–148
Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277:93–96
Kelleher RT, Goldberg SR (1976) General introduction: control of drug-taking behavior by schedules of reinforcement. Pharmacol Rev 27[3]:291–300
Kleven MS, Anthony EW, Woolverton WL (1990) Pharmacological characterization of the discriminative stimulus effects of cocaine in rhesus monkeys. J Pharmacol Exp Ther 254:312–317
Koe BK (1976) Molecular geometry of inhibitors of the uptake of catecholamines and serotonin in synaptosomal preparations of rat brain. J Pharmacol Exp Ther 199:649–661
Koob GF, Le HT, Creese I (1987) The D1 dopamine receptor antagonist SCH 23390 increases cocaine self-administration in the rat. Neurosci Lett 79:315–320
Melia KF, Spealman RD (1991) Pharmacological characterization of the discriminative stimulus effects of GBR 12909. J Pharmacol Exp Ther 258:626–632
Murray AM, Waddington JL (1989) The induction of grooming and vacuous chewing by a series of selective D1 dopamine receptor agonists: two directions of D1: D2 interaction. Eur J Pharmacol 160:377–384
O'Boyle KM, Waddington JL (1992) Agonist and antagonist interactions with D1 dopamine receptors: agonist-induced masking of D1 receptors depends on intrinsic activity. Neuropharmacology 31:177–183
O'Boyle KM, Gaitanopoulos DE, Brenner M, Waddington JL (1989) Agonist and antagonist properties of benzazepine and thienopyridine derivatives at the D1 dopamine receptor. Neuropharmacology 28:401–405
Pellon R, Flores P, Alling K, Witkin JM, Katz JL (1995) Pharmacological analysis of the scratching produced by dopamine D2 agonists in squirrel monkeys. J Pharmacol Exp Ther 271:138–145
Pfeiffer FR, Wilson JW, Weinstock J, Kuo GY, Chambers PA, Holden KG, Hahn RA, Wardell JR, Tobia AJ, Setler PE, Sarau HM (1982) Dopaminergic activity of substituted 6-chloro-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines. J Med Chem 25:352–358
Raiteri M, Bertollini A, Angelini F, Levi G (1975)d-Amphetamine as a releaser or reuptake inhibitor of biogenic amines in synaptosomes. Eur J Pharmacol 34:189–195
Reith MEA, Meisler BE, Sershen H, Lajtha A (1986) Structural requirements for cocaine cogeners to interact with dopamine and serotonin uptake sites in mouse brain and to induce stereotyped behaviors. Biochem Pharmacol 35:1123–1129
Rosengarten J, Schweitzer JW, Friedhoff AJ (1983) Induction of oral dyskinesia in naive by D1 stimulation. Life Sci 33: 2479–2482
Rosenzweig-Lipson S, Bergman J (1993a) Modification of the behavioral effects of the dopamine D2 agonist (+)-4-propyl-9-hydroxynapthoxazine by dopamine antagonists in monkeys. J Pharmacol Exp Ther 265:1039–1046
Rosenzweig-Lipson S, Bergman J (1993b) Dopamine D1 receptor involvement in the discriminative stimulus effects of SKF 81297 in squirrel monkeys. J Pharmacol Exp Ther 267:765–775
Rosenzweig-Lipson S, Hesterberg P, Bergman J (1994a) Observational studies of dopamine D1 and D2 agonists in squirrel monkeys. Psychopharmacology 116:9–18
Rosenzweig-Lipson S, Madras BK, Spealman RD, Bergman J (1994b) Comparison of the behavioral effects of SKF 81297, SKF 82958 and cocaine in squirrel monkeys. NIDA Res Monogr 141:285
Schwartz JC, Giros B, Martres MP, Sokoloff P (1992) The dopamine receptor family: molecular biology and pharmacology. Neurosciences 4:99–108
Self DW, Stein L (1992) The D1 agonists SKF 82958 and SKF 77434 are self-administered by rats. Brain Res 582:349–352
Spealman RD, Kelleher RT (1979) Behavioral effects of self-administered cocaine: responding maintained alternately by cocaine and electric shock in squirrel monkeys. J Pharmacol Exp Ther 210:206–214
Spealman RD, Bergman B, 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
Spealman RD, Bergman J, Madras BK, Kamien JB, Melia KF (1992) Role of D1 and D2 dopamine receptors in the behavioral effects of cocaine. Neurochem Int 20:1475–1525
Terry P, Katz JL (1994) A comparison of the effects of the D1 receptor antagonists SCH 23390 and SCH 39166 on suppression of feeding behavior by the D1 agonist SKF 38393. Psychopharmacology 113:328–333
Tidey J, Bergman J (1996) Efficacy-related differences in behavioral effects of dopamine D1 and D2 agonists. In: Problems of drug dependence 1995. NIDA Res Monogr, US Govt Printing Office, Washington, DC (in press)
Undie AS, Weinstock J, Sarau HM, Friedman E (1994) Evidence for a distinct D1-like dopamine receptor that couples to activation of phosphoinositide metabolism in brain. J Neurochem 62:2045–2048
Vermeulen RJ, Jongenelen CAM, Langeveld CH, Wolters EC, Stoof JC, Drukarch B (1995) Dopamine D1 receptor agonists display a different intrinsic activity in rat, monkey and human astrocytes. Eur J Pharmacol Mol Pharmacol 269:121–125
Weed MR, Vanover KE, Woolverton WL (1993) Reinforcing effects of the D1 dopamine agonist SKF 81297 in rhesus monkeys. Psychopharmacology 113:51–52
Weed MR, Woolverton ML (1995) The reinforcing effects of D1 receptor agonists in rhesus monkeys. J Pharmacol Exp Ther 275:1367–1374
Witkin JM, Nichols DE, Terry P, Katz JL (1991) Behavioral effects of selective dopaminergic compounds in rats discriminating cocaine injections. J Pharmacol Exp Ther 257:706–713
Woodward RM, Panicker MM, Miledi R (1992) Actions of dopamine and dopaminergic drugs on cloned serotonin receptors expressed in Xenopus oocytes. Proc Natl Acad Sci USA 89:4708–4712
Woolverton WL (1986) Effects of a D1 and a D2 dopamine antagonist on the self-administration of cocaine and piribedil by rhesus monkeys. Pharmacol Biochem Behav 24:531–535
Woolverton WL, Goldberg LI, Ginos JZ (1984) Intravenous self-administration of dopamine receptor agonists by rhesus monkeys. J Pharmacol Exp Ther 229:678–683
Yokel RA, Wise RA (1978) Amphetamine-type reinforcement by dopaminergic agonists in the rat. Psychopharmacology 58:289–296
Young AM, Woods JH (1981) Maintenance of behavior by ketamine and related compounds in rhesus monkeys with different self-administration histories. J Pharmacol Exp Ther 218:720–727
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Grech, D.M., Spealman, R.D. & Bergman, J. Self-administration of D1 receptor agonists by squirrel monkeys. Psychopharmacology 125, 97–104 (1996). https://doi.org/10.1007/BF02249407
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DOI: https://doi.org/10.1007/BF02249407
Key words
- Cocaine
- Dopamine
- Fixed-ratio
- (+)-PHNO [(+)-4-propyl-9-hydroxynaphthoxazine]
- Quinpirole
- Second-order
- Self-administration
- SKF 82958 [R,S-6-chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine]
- SKF 81297 [R,S-6-chloro-7, 8-dihydroxy-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine]
- SKF 77434 [R,S-7, 8-dihydroxy-3-allyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine]
- Squirrel monkey
- D1 agonist
- D2 agonist