Skip to main content
SpringerLink
Log in

Role of dopamine D1 receptors in the prefrontal dorsal agranular insular cortex in mediating cocaine self-administration in rats

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Orbital/insular areas of the prefrontal cortex (PFC) are implicated in cocaine addiction. However, the role of dopamine D1 receptors in mediating cocaine self-administration in these sub-regions remains unknown.

Objectives

To define the role of the dorsal agranular insular (AId) sub-region of the PFC, we investigated the effects of D1 receptor manipulation on self-administration behavior maintained by cocaine and cocaine-related stimuli.

Materials and methods

Rats were trained to lever press for cocaine (1 mg/kg) under a fixed-interval 5-min (fixed-ratio 5:S) second-order schedule of reinforcement in the presence of conditioned light cues and contextual sound cues. Intra-AId infusions of vehicle, the D1-like receptor agonist SKF 81297 (0.1, 0.2, 0.4 μg/side) or the D1-like receptor antagonist SCH 23390 (1.0, 2.0, 4.0 μg/side), were administered prior to 1-h self-administration test sessions. Food-maintained responding under a second-order schedule was examined in separate rats to determine if pretreatment with D1 ligands produced general impairments in responding.

Results

Infusion of SKF 81297 (0.2 and 0.4 μg/side) reduced active lever responses during the first 30 min of 1-h test sessions, but did not influence cocaine intake. Infusion of 4.0 μg/side SCH 23390 reduced active lever responses and cocaine intake throughout the 1-h test sessions. Additionally, this dose of SCH 23390 disrupted food-maintained responding and intake.

Conclusions

D1 receptor agonists and antagonists in the AId have diverse consequences and time courses of action. D1 receptor stimulation in the AId may reduce the motivating influence of cocaine-related stimuli on responding whereas D1 receptor blockade in this PFC sub-region produces global disruptions in behavior.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

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

    Article  PubMed  CAS  Google Scholar 

  • Alleweireldt AT, Kirschner KF, Blake CB, Neisewander JL (2003) D1-receptor drugs and cocaine-seeking behavior: investigation of receptor mediation and behavioral disruption in rats. Psychopharmacology 168:109–117

    Article  PubMed  CAS  Google Scholar 

  • Alleweireldt AT, Hobbs RJ, Taylor AR, Neisewander JL (2006) Effects of SCH-23390 infused into the amygdala or adjacent cortex and basal ganglia on cocaine seeking and self-administration in rats. Neuropsychopharmacology 31:363–374

    Article  PubMed  CAS  Google Scholar 

  • Anderson SM, Bari AA, Pierce RC (2003) Administration of the D1-like dopamine receptor antagonist SCH-23390 into the medial nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug-seeking behavior in rats. Psychopharmacology 168:132–138

    Article  PubMed  CAS  Google Scholar 

  • Arroyo M, Markou A, Robbins TW, Everitt BJ (1998) Acquisition, maintenance and reinstatement of intravenous cocaine self-administration under a second-order schedule of reinforcement in rats: effects of conditioned cues and continuous access to cocaine. Psychopharmacology 140:331–344

    Article  PubMed  CAS  Google Scholar 

  • Bachtell RK, Whisler K, Karanian D, Self DW (2005) Effects of intra-nucleus accumbens shell administration of dopamine agonists and antagonists on cocaine-taking and cocaine-seeking behaviors in the rat. Psychopharmacology 183:41–53

    Article  PubMed  CAS  Google Scholar 

  • Barrett AC, Miller JR, Dohrmann JM, Caine SB (2004) Effects of dopamine indirect agonists and selective D1-like and D2-like agonists and antagonists on cocaine self-administration and food maintained responding in rats. Neuropharmacology 47:256–273

    Article  PubMed  CAS  Google Scholar 

  • Berglind WJ, Case JM, Parker MP, Fuchs RA, See RE (2006) Dopamine D1 or D2 receptor antagonism within the basolateral amygdala differentially alters the acquisition of cocaine-cue associations necessary for cue-induced reinstatement of cocaine-seeking. Neuroscience 137:699–706

    Article  PubMed  CAS  Google Scholar 

  • Brady LS, Barrett JE (1985) Effects of serotonin receptor agonists and antagonists on schedule-controlled behavior of squirrel monkeys. J Pharmacol Exp Ther 235(2):436–441

    PubMed  CAS  Google Scholar 

  • Caine SB, Negus SS, Mello NK, Bergman J (1999) Effects of dopamine D(1-like) and D(2-like) agonists in rats that self-administer cocaine. J Pharmacol Exp Ther 291:353–360

    PubMed  CAS  Google Scholar 

  • Caine SB, Negus SS, Mello NK (2000) Effects of dopamine D(1-like) and D(2-like) agonists on cocaine self-administration in rhesus monkeys: rapid assessment of cocaine dose–effect functions. Psychopharmacology 148:41–51

    Article  PubMed  CAS  Google Scholar 

  • Crombag HS, Grimm JW, Shaham Y (2002) Effect of dopamine receptor antagonists on renewal of cocaine seeking by reexposure to drug-associated contextual cues. Neuropsychopharmacology 27:1006–1015

    Article  PubMed  CAS  Google Scholar 

  • Di Pietro NC, Black YD, Green-Jordan K, Eichenbaum HB, Kantak KM (2004) Complementary tasks to measure working memory in distinct prefrontal cortex subregions in rats. Behav Neurosci 118:1042–1051

    Article  PubMed  Google Scholar 

  • Di Pietro NC, Black YD, Kantak KM (2006) Context-dependent prefrontal cortex regulation of cocaine self-administration and reinstatement behaviors in rats. Eur J Neurosci 24:3285–3298

    Article  PubMed  Google Scholar 

  • Everitt BJ, Robbins TW (2000) Second-order schedules of drug reinforcement in rats and monkeys: measurement of reinforcing efficacy and drug-seeking behaviour. Psychopharmacology 153:17–30

    Article  PubMed  CAS  Google Scholar 

  • Floresco SB, Phillips AG (2001) Delay-dependent modulation of memory retrieval by infusion of a dopamine D1 agonist into the rat medial prefrontal cortex. Behav Neurosci 115:934–939

    Article  PubMed  CAS  Google Scholar 

  • Fuchs RA, Evans KA, Parker MP, See RE (2004) Differential involvement of orbitofrontal cortex subregions in conditioned cue-induced and cocaine-primed reinstatement of cocaine seeking in rats. J Neurosci 24:6600–6610

    Article  PubMed  CAS  Google Scholar 

  • Fuchs R, Evans KA, Ledford CC, Parker MP, Case JM, Mehta RH, See RE (2005) The role of the dorsomedial prefrontal cortex, basolateral amygdala, and dorsal hippocampus in contextual reinstatement of cocaine seeking in rats. Neuropsychopharmacology 30:296–309

    Article  PubMed  CAS  Google Scholar 

  • Gallagher M, McMahan RW, Schoenbaum G (1999) Orbitofrontal cortex and representation of incentive value in associative learning. J Neurosci 19:6610–6614

    PubMed  CAS  Google Scholar 

  • Glowa JR, Wojnicki FH (1996) Effects of drugs on food- and cocaine-maintained responding, III: Dopaminergic antagonists. Psychopharmacology 128:351–358

    Article  PubMed  CAS  Google Scholar 

  • Goeders NE, Smith JE (1983) Cortical dopaminergic involvement in cocaine reinforcement. Science 221:773–775

    Article  PubMed  CAS  Google Scholar 

  • Goeders NE, Smith JE (1986) Reinforcing properties of cocaine in the medical prefrontal cortex: primary action on presynaptic dopaminergic terminals. Pharmacol Biochem Behav 25:191–199

    Article  PubMed  CAS  Google Scholar 

  • Goeders NE, Dworkin SI, Smith JE (1986) Neuropharmacological assessment of cocaine self-administration into the medial prefrontal cortex. Pharmacol Biochem Behav 24:1429–1440

    Article  PubMed  CAS  Google Scholar 

  • Ito R, Dalley JW, Howes SR, Robbins TW, Everitt BJ (2000) Dissociation in conditioned dopamine release in the nucleus accumbens core and shell in response to cocaine cues and during cocaine-seeking behavior in rats. J Neurosci 20(19):7489–7495

    PubMed  CAS  Google Scholar 

  • Jackson ME, Moghaddam B (2001) Amygdala regulation of nucleus accumbens dopamine output is governed by the prefrontal cortex. J Neurosci 21:676–681

    PubMed  CAS  Google Scholar 

  • Jackson ME, Frost AS, Moghaddam B (2001) Stimulation of prefrontal cortex at physiologically relevant frequencies inhibits dopamine release in the nucleus accumbens. J Neurochem 78:920–923

    Article  PubMed  CAS  Google Scholar 

  • Kantak KM, Collins SL, Lipman EG, Bond J, Giovanoni K, Fox BS (2000) Evaluation of anti-cocaine antibodies and a cocaine vaccine in a rat self-administration model. Psychopharmacology 148:251–262

    Article  PubMed  CAS  Google Scholar 

  • Kantak KM, Black Y, Valencia E, Green-Jordan K, Eichenbaum HB (2002a) 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

    PubMed  CAS  Google Scholar 

  • Kantak KM, Black Y, Valencia E, Green-Jordan K, Eichenbaum HB (2002b) Stimulus–response functions of the lateral dorsal striatum and regulation of behavior studied in a cocaine maintenance/cue reinstatement model in rats. Psychopharmacology 161:278–287

    Article  PubMed  CAS  Google Scholar 

  • Kantak KM, Udo T, Ugalde F, Luzzo C, Di Pietro N, Eichenbaum HB (2005) Influence of cocaine self-administration on learning related to prefrontal cortex or hippocampus functioning in rats. Psychopharmacology 181:227–236

    Article  PubMed  CAS  Google Scholar 

  • Khroyan TV, Barrett-Larimore RL, Rowlett JK, Spealman RD (2000) Dopamine D1- and D2-like receptor mechanisms in relapse to cocaine-seeking behavior: effects of selective antagonists and agonists. J Pharmacol Exp Ther 294:680–687

    PubMed  CAS  Google Scholar 

  • Khroyan TV, Platt DM, Rowlett JK, Spealman RD (2003) Attenuation of relapse to cocaine seeking by dopamine D1 receptor agonists and antagonists in non-human primates. Psychopharmacology 168:124–131

    Article  PubMed  CAS  Google Scholar 

  • King D, Zigmond MJ, Finlay JM (1997) Effects of dopamine depletion in the medial prefrontal cortex on the stress-induced increase in extracellular dopamine in the nucleus accumbens core and shell. Neuroscience 77:141–153

    Article  PubMed  CAS  Google Scholar 

  • Kuzhikandathil EV, Oxford GS (2002) Classic D1 dopamine receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl- 2,3,4,5-tetrahydro-1H-3-benzaze pine hydrochloride (SCH23390) directly inhibits G protein-coupled inwardly rectifying potassium channels. Mol Pharmacol 62:119–126

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • McGregor A, Roberts DC (1993) Dopaminergic antagonism within the nucleus accumbens or the amygdala produces differential effects on intravenous cocaine self-administration under fixed and progressive ratio schedules of reinforcement. Brain Res 624:245–252

    Article  PubMed  CAS  Google Scholar 

  • McKearney JW (1990) Effects of serotonin agonists on operant behavior in the squirrel monkey: quipazine, MK-212, trifluoromethylphenylpiperazine, and chlorophenylpiperazine. Pharmacol Biochem Behav 35(1):181–185

    Article  PubMed  CAS  Google Scholar 

  • McLaughlin J, See RE (2003) Selective inactivation of the dorsomedial prefrontal cortex and the basolateral amygdala attenuates conditioned-cued reinstatement of extinguished cocaine-seeking behavior in rats. Psychopharmacology 168:57–65

    Article  PubMed  CAS  Google Scholar 

  • Millan MJ, Newman-Tancredi A, Quentric Y, Cussac D (2001) The ‘selective’ dopamine D1 receptor antagonist, SCH23390, is a potent and high efficacy agonist at cloned human serotonin2C receptors. Psychopharmacology 156:58–62

    Article  PubMed  CAS  Google Scholar 

  • Mutschler NH, Bergman J (2002) Effects of chronic administration of the D1 receptor partial agonist SKF 77434 on cocaine self-administration in rhesus monkeys. Psychopharmacology 160:362–370

    Article  PubMed  CAS  Google Scholar 

  • Olsen CM, Duvauchelle CL (2006) Prefrontal cortex D1 modulation of the reinforcing properties of cocaine. Brain Res 1075:229–235

    Article  PubMed  CAS  Google Scholar 

  • Platt DM, Rowlett JK, Spealman RD (2001) Modulation of cocaine and food self-administration by low- and high-efficacy D1 agonists in squirrel monkeys. Psychopharmacology 157:208–216

    Article  PubMed  CAS  Google Scholar 

  • Porrino LJ, Lyons D, Miller MD, Smith HR, Friedman DP, Daunais JB, Nader MA (2002) Metabolic mapping of the effects of cocaine during the initial phases of self-administration in the nonhuman primate. J Neurosci 22:7687–7694

    PubMed  CAS  Google Scholar 

  • Sanchez CJ, Bailie TM, Wu WR, Li N, Sorg BA (2003) Manipulation of dopamine D1-like receptor activation in the rat medial prefrontal cortex alters stress- and cocaine-induced reinstatement of conditioned place preference behavior. Neuroscience 119:497–505

    Article  PubMed  CAS  Google Scholar 

  • Schindler CW, Panlilio LV, Goldberg SR (2002) Second-order schedules of drug self-administration in animals. Psychopharmacology 163:327–344

    Article  PubMed  CAS  Google Scholar 

  • Schmidt HD, Anderson SM, Pierce RC (2006) Stimulation of D1-like or D2 dopamine receptors in the shell, but not the core, of the nucleus accumbens reinstates cocaine-seeking behaviour in the rat. Eur J Neurosci 23:219–228

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Sorg BA, Li N, Wu WR (2001) Dopamine D1 receptor activation in the medial prefrontal cortex prevents the expression of cocaine sensitization. J Pharmacol Exp Ther 297:501–508

    PubMed  CAS  Google Scholar 

  • Sun W, Rebec GV (2005) The role of prefrontal cortex D1-like and D2-like receptors in cocaine-seeking behavior in rats. Psychopharmacology 177:315–323

    Article  PubMed  CAS  Google Scholar 

  • Thompson TL, Moss RL (1995) In vivo stimulated dopamine release in the nucleus accumbens: modulation by the prefrontal cortex. Brain Res 686:93–98

    Article  PubMed  CAS  Google Scholar 

  • Volkow ND, Fowler JS (2000) Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cereb Cortex 10:318–325

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Weissenborn R, Robbins TW, Everitt BJ (1997) Effects of medial prefrontal or anterior cingulate cortex lesions on responding for cocaine under fixed-ratio and second-order schedules of reinforcement in rats. Psychopharmacology 134:242–257

    Article  PubMed  CAS  Google Scholar 

  • Woolverton WL, Virus RM (1989) The effects of a D1 and a D2 dopamine antagonist on behavior maintained by cocaine or food. Pharmacol Biochem Behav 32:691–697

    Article  PubMed  CAS  Google Scholar 

  • Wright CI, Groenewegen HJ (1996) Patterns of overlap and segregation between insular cortical, intermediodorsal thalamic and basal amygdaloid afferents in the nucleus accumbens of the rat. Neuroscience 73(2):359–373

    Article  PubMed  CAS  Google Scholar 

  • Zahrt J, Taylor JR, Mathew RG, Arnsten AF (1997) Supranormal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory performance. J Neurosci 17:8528–8535

    PubMed  CAS  Google Scholar 

Download references

Acknowledgment

Grant Number R01DA011716 from the National Institute on Drug Abuse supported the project described. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute On Drug Abuse or the National Institutes of Health.

Author information

Authors and Affiliations

  1. Laboratory of Behavioral Neuroscience, Department of Psychology and Program in Neuroscience, Boston University, 64 Cummington St., Boston, MA, 02215, USA

    Nina C. Di Pietro, Yasmin Mashhoon, Chelcie Heaney, Lindsay M. Yager & Kathleen M. Kantak

Authors
  1. Nina C. Di Pietro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasmin Mashhoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chelcie Heaney
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lindsay M. Yager
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kathleen M. Kantak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kathleen M. Kantak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Di Pietro, N.C., Mashhoon, Y., Heaney, C. et al. Role of dopamine D1 receptors in the prefrontal dorsal agranular insular cortex in mediating cocaine self-administration in rats. Psychopharmacology 200, 81–91 (2008). https://doi.org/10.1007/s00213-008-1149-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-008-1149-0

Keywords

Search

Navigation