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D1-receptor drugs and cocaine-seeking behavior: investigation of receptor mediation and behavioral disruption in rats

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Abstract

Rationale.

Dopamine D1-receptor antagonists and agonists both attenuate cocaine-seeking behavior (i.e., operant responding in the absence of cocaine reinforcement) elicited by a cocaine prime or cocaine-paired stimuli. It remains unclear whether these effects are D1-receptor mediated.

Objectives.

The present study tested whether a D1 antagonist (SCH-23390) would reverse the attenuating effects of a D1 agonist (SKF-81297) on cocaine-seeking behavior and whether behavioral disruption is involved in these effects.

Methods.

Rats trained to press a lever for cocaine reinforcement with light and tone cues paired with each infusion underwent daily extinction sessions during which responding had no scheduled consequences (i.e., neither cocaine nor the cocaine-paired stimulus complex was available). After responding diminished, the effects of the D1 antagonist on the dose–response functions of the D1 agonist for reinstatement of cocaine-seeking behavior by response-contingent cue presentations or cocaine priming were examined. A separate experiment assessed the effects of the agonist on the dose–response function of the antagonist for cue reinstatement. Stereotyped behavior and activity were also measured during each test session.

Results.

The attenuating effects of SKF-81297 on cocaine-seeking behavior during cocaine-primed reinstatement were reversed by co-administration of SCH-23390. However, no evidence for reversal of the attenuation during cue reinstatement was found even though agonist-induced stereotypy and antagonist-induced hypoactivity were reversed by co-administration of the two drugs during the same test session.

Conclusions.

The findings suggest that the attenuating effects of D1-receptor drugs on cocaine-seeking behavior during cocaine reinstatement are mediated by dopamine D1 receptors; however, it remains unclear whether the effects of these drugs on cocaine-seeking behavior during cue reinstatement are D1-receptor mediated. Nevertheless, it is evident that the attenuation of cocaine-seeking behavior by these drugs is not simply due to behavioral disruption.

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References

  • Alleweireldt AT, Weber SM, Kirschner KF, Bullock BL, Neisewander JL (2002) Blockade or stimulation of D1 dopamine receptors attenuates cue reinstatement of extinguished cocaine-seeking behavior in rats. Psychopharmacology 159:284–293

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

  • Baker DA, Tran-Nguyen LTL, Fuchs RA, Neisewander JL (2001) Influence of individual differences and chronic fluoxetine treatment on cocaine-seeking behavior in rats. Psychopharmacology 155:18–26

  • Beninger RJ, Rolfe NG (1995) Dopamine D1-like receptor agonists impair responding for conditioned reward in rats. Behav Pharmacol 3:155–163

  • Caprilles N, Amir S, Stewart J (2001) Inactivation of prefrontal and orbitofrontal regions by tetrodotoxin attenuates stress-induced reinstatement of cocaine seeking. Soc Neurosci Abstr 27:442.2

  • Carroll ME, France CP, Meisch RA (1981) Intravenous self-administration of etonitazene, cocaine and phencyclidine in rats during food deprivation and satiation. J Pharmacol Exp Ther 217:241–247

  • Childress A, Ehrman R, McLellan AT, O'Brien C (1988) Conditioned craving and arousal in cocaine addiction: a preliminary report. NIDA Res Monogr 81:74–80

  • Ciccocioppo R, Sanna PP, Weiss F (2001) Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: reversal by D(1) antagonists. Proc Natl Acad Sci USA 98:1976–1981

  • Dawson TM, Gehlert DR, McCabe RT, Barnett A, Wamsley JK (1986) D-1 dopamine receptors in the rat brain: a quantitative autoradiographic analysis. J Neurosci 6:2352–2365

  • Deroche V, Le Moal M, Piazza PV (1999) Cocaine self-administration increases the incentive motivational properties of the drug in rats. Eur J Neurosci 11:2731–2736

  • de Wit H, Stewart J (1981) Reinstatement of cocaine-reinforced responding in the rat. Psychopharmacology 75:134–143

  • Fuchs RA, Tran-Nguyen LTL, Specio SE, Groff RS, Neisewander JL (1998) Predictive validity of the extinction/reinstatement model of drug craving. Psychopharmacology 135:151–160

  • Fuchs RA, Weber SM, Rice HJ, Neisewander JL (2002) Effects of excitotoxic lesions of the basolateral amygdala on cocaine-seeking behavior and cocaine conditioned place preference in rats. Brain Res 929:15–25

  • Grimm JW, See RE (2000) Dissociation of primary and secondary reward-relevant limbic nuclei in an animal model of relapse. Neuropsychopharmacology 22:473–479

  • Haney M, Collins ED, Ward AS, Foltin RW, Fischman MW (1999) Effect of a selective dopamine D1 agonist (ABT-431) on smoked cocaine self-administration in humans. Psychopharmacology 143:102–110

  • Jin L, Wang H, Friedman E (2001) Stimulated D1 dopamine receptors couple to multiple Gα proteins in different brain regions. J Neurochem 78:981–990

  • Kantak KM, Black Y, Valencia E, Green-Jordan K, Eichenbaum HB (2002) Dissociable effects of lidocaine inactivation of the rostral and caudal basolateral amygdala on the maintenance and reinstatement of cocaine-seeking behavior in rats. J Neurosci 22:1126–1136

  • Kennedy LT, Hanbauer I (1983) Sodium-sensitive cocaine binding to rat striatal membrane: possible relationship to dopamine uptake sites. J Neurochem 41:172–178

  • Keppel G (1991) Design and analysis: a researcher's handbook, 3rd edn. Prentice Hall, Upper Saddle River, pp 169–170

  • Khroyan TV, Barrett-Larimore RL, Rowlett JK, Apealman RD (2000) Dopamine D1- and D1-like receptor mechanisms in relapse to cocaine-seeking behavior: effects of selective antagonists and agonists. J Pharmacol Exp Ther 294:680–687

  • Kilts CD, Anderson CM, Ely TD, Mailman RB (1988) The biochemistry and pharmacology of mesoamygdaloid dopamine neurons. Ann NY Acad Sci 537:173–187

  • Lavin A, Grace AA (2001) Stimulation of D1-type dopamine receptors enhances excitability in prefrontal cortical pyramidal neurons in a state-dependent manner. Neuroscience 104:335–346

  • Lewis BL, O'Donnell P (2000) Ventral tegmental area afferents to the prefrontal cortex maintain membrane potential 'up' states in pyramidal neurons via D(1) dopamine receptors. Cereb Cortex 10:1168–1175

  • Markou A, Weiss F, Gold LH, Caine B, Schulteis G, Koob GF (1993) Animal models of drug craving. Psychopharmacology 112:163–182

  • McFarland K, Kalivas PW (2001) The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior. J Neurosci 21:8655–8663

  • Meil WM, See RE (1997) Lesions of the basolateral amygdala abolish the ability of drug associated cues to reinstate responding during withdrawal from self-administered cocaine. Behav Brain Res 87:139–148

  • Mowrer OH, Jones H (1945) Habit strength as a function of the pattern of reinforcement. J Exp Psychol 35:293–311

  • Neisewander JL, Baker DA, Fuchs RA, Tran-Nguyen LT, Palmer A, Marshall JF (2000) Fos protein expression and cocaine-seeking behavior in rats after exposure to a cocaine self-administration environment. J Neurosci 20:798–805

  • Pacheco MA, Jope RS (1997) Comparison of [3H] phosphatidylinositol and [3H]phosphatidylinositol 4,5-biphosphate hydrolysis in postmortem human brain membranes and characterization of stimulation by dopamine D1 receptors. J Neurochem 69:639–644

  • Park WK, Bari AA, Jey AR, Anderson SM, Spealman RD, Rowlett JK, Pierce RC (2002) Cocaine administered into the medial prefrontal cortex reinstates cocaine-seeking behavior by increasing AMPA receptor-mediated glutamate transmission in the nucleus accumbens. J Neurosci 22:2916–2925

  • Ranaldi R, Beninger RJ (1993) Dopamine D1 and D2 antagonists attenuate amphetamine-produced enhancement of responding for conditioned reward in rats. Psychopharmacology 113:110–118

  • Ranaldi R, Pantalony D, Beninger RJ (1995) The D1 agonist SKF-38393 attenuates amphetamine-produced enhancement of responding for conditioned reward in rats. Pharmacol Biochem Behav 52:131–137

  • Romach MK, Glue P, Kampman K, Kaplan HL, Somer GR, Poole S, Clarke L, Coffin V, Cornish J, O'Brien CP, Sellers EM (1999) Attenuation of the euphoric effects of cocaine by the dopamine D1/D5 antagonist ecopipam (SCH 39166). Arch Gen Psychiatry 56:1101–1106

  • See RE, Kruzich PJ, Grimm JW (2001) Dopamine, but not glutamate, receptor blockade in the basolateral amygdala attenuates conditioned reward in a rat model of relapse to cocaine-seeking behavior. Psychopharmacology 154:301–310

  • Self DW, Barnhart WJ, Lehman DA, Nestler EJ (1996) Opposite modulation of cocaine-seeking behavior by D1- and D2-like dopamine receptor agonists. Science 271:1586–1589

  • Self DW, Karanian DA, Spencer JJ (2000) Effects of the novel D1 dopamine receptor agonist ABT-431 on cocaine self-administration and reinstatement. Ann NY Acad Sci 909:133–144

  • Sutton MA, Beninger RJ (1999) Psychopharmacology of conditioned reward: evidence for a rewarding signal at D1-like dopamine receptors. Psychopharmacology 144:95–110

  • Undie AS (1999) Relationship between dopamine agonist stimulation of inositol phosphate formation and cytidine diphosphate-diacylglycerol accumulation in brain slices. Brain Res 816:286–294

  • 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

  • Wallace BC (1989) Psychological and environmental determinants of relapse in crack cocaine smokers. J Subst Abuse Treat 6:95–106

  • Wang HY, Undie AS, Friedman E (1995) Evidence for the coupling of Gq protein to D1-like dopamine sites in rat striatum: possible role in dopamine-mediated inositol phosphate formation. Mol Pharmacol 48:988–994

  • Weissenborn R, Deroche V, Koob GF, Weiss F (1996) Effects of dopamine agonists and antagonists on cocaine-induced operant responding for a cocaine-associated stimulus. Psychopharmacology 126:311–322

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Acknowledgements.

The authors thank Thomas Shepherd and Jeffrey Burmeister for their expert technical assistance and Dr. Brock Schroeder for his comments on a previous version of this manuscript. This research was supported by grants from NIDA, DA11064 and DA06095.

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Correspondence to Janet L. Neisewander.

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Alleweireldt, A.T., Kirschner, K.F., Blake, C.B. et al. D1-receptor drugs and cocaine-seeking behavior: investigation of receptor mediation and behavioral disruption in rats. Psychopharmacology 168, 109–117 (2003). https://doi.org/10.1007/s00213-002-1305-x

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  • DOI: https://doi.org/10.1007/s00213-002-1305-x

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