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Effects of dopamine receptor antagonism and amphetamine-induced psychomotor sensitization on sign- and goal-tracking after extended training


Effects of dopamine receptor antagonism and amphetamine-induced psychomotor sensitization on sign- and goal-tracking after extended training

Khoo, Shaun Yon-Seng ORCID: https://orcid.org/0000-0002-0972-3788, Uhrig, Alexandra, Samaha, Anne-Noël ORCID: https://orcid.org/0000-0001-5546-1910 and Chaudhri, Nadia ORCID: https://orcid.org/0000-0003-4217-4044 (2021) Effects of dopamine receptor antagonism and amphetamine-induced psychomotor sensitization on sign- and goal-tracking after extended training. Behavioural Brain Research . ISSN 0166-4328

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Official URL: https://doi.org/10.1016/j.bbr.2021.113238


The dopamine system is important for incentive salience attribution, where motivational value is assigned to conditioned cues that predict appetitive reinforcers. However, the role of dopamine in this process may change with extended training. We tested the effects of dopamine D1-like and D2-like receptor antagonism on the expression of sign-tracking and goal-tracking conditioned responses following extended Pavlovian conditioned approach (PCA) training. We also tested if amphetamine-induced psychomotor sensitization accelerates the enhanced acquisition of sign-tracking that is observed with extended training. In experiment 1, 24 male Long-Evans rats received 20 PCA sessions in which one lever (CS+, 10 s) predicted 0.2 mL sucrose (10\%, w/v) delivery and the other lever (CS–) did not. SCH-23390 (D1-like antagonist) or eticlopride (D2-like antagonist) were administered before non-reinforced behavioural tests at doses of 0, 0.01, and 0.1 mg/kg (s.c.). In experiment 2, rats received vehicle or 2 mg/kg amphetamine (i.p.) for 7 days (n = 12/group). Ten days later, they received 16 PCA training sessions. Both doses of SCH-23390 reduced sign- and goal-tracking, but also reduced locomotor behaviour. A low dose of eticlopride (0.01 mg/kg) selectively reduced goal-tracking, without affecting sign-tracking or locomotor behaviour. Amphetamine produced psychomotor sensitization, and this did not affect the acquisition of sign- or goal-tracking. Following extended PCA training, dopamine D2-like receptor activity is required for the expression of goal-tracking but not sign-tracking. Psychomotor sensitization to amphetamine did not impact incentive salience attribution; however, more selective manipulations of the dopamine system may be needed.

Divisions:Concordia University > Research Units > Centre for Studies in Behavioural Neurobiology
Item Type:Article
Authors:Khoo, Shaun Yon-Seng and Uhrig, Alexandra and Samaha, Anne-Noël and Chaudhri, Nadia
Journal or Publication:Behavioural Brain Research
Date:17 March 2021
  • Canadian Institutes of Health Research
  • Natural Sciences and Engineering Research Council
  • Fonds de la recherche du Québec – Santé
  • Concordia University
Digital Object Identifier (DOI):10.1016/j.bbr.2021.113238
Keywords:Autoshaping; Pavlovian conditioned approach; sign-tracking; SCH-23390; eticlopride; amphetamine
ID Code:988082
Deposited On:01 Apr 2021 21:23
Last Modified:01 Apr 2021 21:23
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Ahrens AM, Singer BF, Fitzpatrick CJ, Morrow JD, Robinson TE (2016) Rats that sign-track are resistant to Pavlovian but not instrumental extinction Behavioural Brain Research 296:418-430 doi:10.1016/j.bbr.2015.07.055
Anderson RI, Bush PC, Spear LP (2013) Environmental manipulations alter age differences in attribution of incentive salience to reward-paired cues Behavioural Brain Research 257:83-89 doi:10.1016/j.bbr.2013.09.021
Aoyama K, Barnes J, Koerber J, Glueck E, Dorsey K, Eaton L, Grimm JW (2016) Systemic injection of the DAD1 antagonist SCH 23390 reduces saccharin seeking in rats Appetite 105:8-13 doi:10.1016/j.appet.2016.05.008
Badiani A, Anagnostaras SG, Robinson TE (1995a) The development of sensitization to the psychomotor stimulant effects of amphetamine is enhanced in a novel environment Psychopharmacology 117:443-452 doi:10.1007/BF02246217
Badiani A, Browman KE, Robinson TE (1995b) Influence of novel versus home environments on sensitization to the psychomotor stimulant effects of cocaine and amphetamine Brain Research 674:291-298 doi:10.1016/0006-8993(95)00028-O
Bédard AM, Maheux J, Lévesque D, Samaha AN (2011) Continuous, but not intermittent, antipsychotic drug delivery intensifies the pursuit of reward cues Neuropsychopharmacology 36:1248-1259 doi:10.1038/npp.2011.10
Berridge KC (2007) The debate over dopamine’s role in reward: the case for incentive salience Psychopharmacology 191:391-431 doi:10.1007/s00213-006-0578-x
Berridge KC, Robinson TE (2003) Parsing reward Trends in Neurosciences 26:507-513 doi:10.1016/S0166-2236(03)00233-9
Bradberry CW (2007) Cocaine sensitization and dopamine mediation of cue effects in rodents, monkeys, and humans: areas of agreement, disagreement, and implications for addiction Psychopharmacology 191:705-717 doi:10.1007/s00213-006-0561-6
Campus P et al. (2019) The paraventricular thalamus is a critical mediator of top-down control of cue-motivated behavior in rats eLife 8:e49041 doi:10.7554/eLife.49041
Chaudhri N, Woods CA, Sahuque LL, Gill TM, Janak PH (2013) Unilateral inactivation of the basolateral amygdala attenuates context-induced renewal of pavlovian-conditioned alcohol-seeking European Journal of Neuroscience 38:2751-2761 doi:10.1111/ejn.12278
Chow JJ, Nickell JR, Darna M, Beckmann JS (2016) Toward isolating the role of dopamine in the acquisition of incentive salience attribution Neuropharmacology 109:320-331 doi:10.1016/j.neuropharm.2016.06.028
Clark JJ, Collins AL, Sanford CA, Phillips PEM (2013) Dopamine encoding of Pavlovian incentive stimuli diminishes with extended training The Journal of Neuroscience 33:3526-3532 doi:10.1523/JNEUROSCI.5119-12.2013
Coutts RT, Nazarali AJ, Baker GB, Pasutto FM (1986) Metabolism and disposition of N-(2-cyanoethyl)amphetamine (fenproporex) and amphetamine: study in the rat brain Canadian Journal of Physiology and Pharmacology 64:724-728 doi:10.1139/y86-122
Crombag HS, Badiani A, Chan J, Dell'Orco J, Dineen SP, Robinson TE (2001) The ability of environmental context to facilitate psychomotor sensitization to amphetamine can be dissociated from its effect on acute drug responsiveness and on conditioned responding Neuropsychopharmacology 24:680-690 doi:10.1016/S0893-133X(00)00238-4
Crombag HS, Badiani A, Maren S, Robinson TE (2000) The role of contextual versus discrete drug-associated cues in promoting the induction of psychomotor sensitization to intravenous amphetamine Behavioural Brain Research 116:1-22 doi:10.1016/S0166-4328(00)00243-6
Downs AW, Eddy NB (1932) The effect of repeated doses of cocaine on the rat Journal of Pharmacology and Experimental Therapeutics 46:199-200
Ericson H, Radesäter AC, Servin E, Magnusson O, Mohringe B (1996) Effects of intermittent and continuous subchronic administration of raclopride on motor activity, dopamine turnover and receptor occupancy in the rat Pharmacology & Toxicology 79:277-286 doi:10.1111/j.1600-0773.1996.tb00009.x
Flagel SB et al. (2011) A selective role for dopamine in stimulus–reward learning Nature 469:53-57 doi:10.1038/nature09588
Flagel SB, Watson SJ, Robinson TE, Akil H (2007) Individual differences in the propensity to approach signals vs goals promote different adaptations in the dopamine system of rats Psychopharmacology 191:599-607 doi:10.1007/s00213-006-0535-8
Fraser KM, Haight JL, Gardner EL, Flagel SB (2016) Examining the role of dopamine D2 and D3 receptors in Pavlovian conditioned approach behaviors Behavioural Brain Research 305:87-99 doi:10.1016/j.bbr.2016.02.022
Fraser KM, Janak PH (2017) Long-lasting contribution of dopamine in the nucleus accumbens core, but not dorsal lateral striatum, to sign-tracking European Journal of Neuroscience 46:2047-2055 doi:10.1111/ejn.13642
Kalivas PW, Stewart J (1991) Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity Brain Research Reviews 16:223-244 doi:10.1016/0165-0173(91)90007-U
Karkhanis AN, Rose JH, Weiner JL, Jones SR (2016) Early-life social isolation stress increases kappa opioid receptor responsiveness and downregulates the dopamine system Neuropsychopharmacology 41:2263-2274 doi:10.1038/npp.2016.21
Khoo SY-S, LeCocq MR, Deyab GE, Chaudhri N (2019) Context and topography determine the role of basolateral amygdala metabotropic glutamate receptor 5 in appetitive Pavlovian responding Neuropsychopharmacology doi:10.1038/s41386-019-0335-6
Khoo SY-S, Uhrig A, Samaha A-N, Chaudhri N (2021) Dataset: Effects of dopamine receptor antagonism and amphetamine-induced psychomotor sensitization on sign- and goal-tracking after extended training Figshare doi:10.6084/m9.figshare.7571813.v2
Koob GF, Le HT, Creese I (1987) The D1 dopamine receptor antagonist SCH 23390 increases cocaine self-administration in the rat Neuroscience Letters 79:315-320 doi:10.1016/0304-3940(87)90451-4
Leyton M (2007) Conditioned and sensitized responses to stimulant drugs in humans Progress in Neuro-Psychopharmacology and Biological Psychiatry 31:1601-1613 doi:10.1016/j.pnpbp.2007.08.027
Leyton M, Vezina P (2013) Striatal ups and downs: Their roles in vulnerability to addictions in humans Neuroscience & Biobehavioral Reviews 37:1999-2014 doi:10.1016/j.neubiorev.2013.01.018
Lokiec F, Rapin JR, Jacquot C, Cohen Y (1978) A comparison of the kinetics of d- and l-amphetamine in the brain of isolated and aggregated rats Psychopharmacology 58:73-77 doi:10.1007/BF00426793
Lopez JC, Karlsson R-M, O'Donnell P (2015) Dopamine D2 modulation of sign and goal tracking in rats Neuropsychopharmacology 40:2096-2102 doi:10.1038/npp.2015.68
Meyer PJ, Lovic V, Saunders BT, Yager LM, Flagel SB, Morrow JD, Robinson TE (2012) Quantifying individual variation in the propensity to attribute incentive salience to reward cues PLOS ONE 7:e38987 doi:10.1371/journal.pone.0038987
Palmatier MI, Kellicut MR, Brianna Sheppard A, Brown RW, Robinson DL (2014) The incentive amplifying effects of nicotine are reduced by selective and non-selective dopamine antagonists in rats Pharmacology Biochemistry and Behavior 126:50-62 doi:10.1016/j.pbb.2014.08.012
Panayi MC, Killcross S (2018) Functional heterogeneity within the rodent lateral orbitofrontal cortex dissociates outcome devaluation and reversal learning deficits eLife 7:e37357 doi:10.7554/eLife.37357
Paulson PE, Robinson TE (1995) Amphetamine-induced time-dependent sensitization of dopamine neurotransmission in the dorsal and ventral striatum: A microdialysis study in behaving rats Synapse 19:56-65 doi:10.1002/syn.890190108
Robinson MJF, Anselme P, Suchomel K, Berridge KC (2015) Amphetamine-induced sensitization and reward uncertainty similarly enhance incentive salience for conditioned cues Behavioral Neuroscience 129:502-511 doi:10.1037/bne0000064
Robinson TE, Becker JB (1986) Enduring changes in brain and behavior produced by chronic amphetamine administration: A review and evaluation of animal models of amphetamine psychosis Brain Research Reviews 11:157-198 doi:10.1016/0165-0173(86)90002-0
Robinson TE, Berridge KC (1993) The neural basis of drug craving: An incentive-sensitization theory of addiction Brain Research Reviews 18:247-291 doi:10.1016/0165-0173(93)90013-P
Robinson TE, Berridge KC (2008) The incentive sensitization theory of addiction: some current issues Philosophical Transactions of the Royal Society B: Biological Sciences 363:3137-3146 doi:10.1098/rstb.2008.0093
Roughley S, Killcross S (2019) Differential involvement of dopamine receptor subtypes in the acquisition of Pavlovian sign-tracking and goal-tracking responses Psychopharmacology doi:10.1007/s00213-019-5169-8
Samaha AN, Reckless GE, Seeman P, Diwan M, Nobrega JN, Kapur S (2008) Less is more: Antipsychotic drug effects are greater with transient rather than continuous delivery Biological Psychiatry 64:145-152 doi:10.1016/j.biopsych.2008.01.010
Schuweiler DR, Athens JM, Thompson JM, Vazhayil ST, Garris PA (2018) Effects of an acute therapeutic or rewarding dose of amphetamine on acquisition of Pavlovian autoshaping and ventral striatal dopamine signaling Behavioural Brain Research 336:191-203 doi:10.1016/j.bbr.2017.09.003
Sciascia JM, Mendoza J, Chaudhri N (2014) Blocking dopamine D1-like receptors attenuates context-induced renewal of pavlovian-conditioned alcohol-seeking in rats Alcoholism: Clinical and Experimental Research 38:418-427 doi:10.1111/acer.12262
Segal DS, Mandell AJ (1974) Long-term administration of d-amphetamine: Progressive augmentation of motor activity and stereotypy Pharmacology Biochemistry and Behavior 2:249-255 doi:10.1016/0091-3057(74)90060-4
Servonnet A, Samaha AN (2020) Antipsychotic-evoked dopamine supersensitivity Neuropharmacology 163:107630 doi:10.1016/j.neuropharm.2019.05.007
Simon NW, Mendez IA, Setlow B (2008) Effects of prior amphetamine exposure on approach strategy in appetitive Pavlovian conditioning in rats Psychopharmacology 202:699-709 doi:10.1007/s00213-008-1353-y
Smith AP, Hofford RS, Zentall TR, Beckmann JS (2018) The role of ‘jackpot’ stimuli in maladaptive decision-making: dissociable effects of D1/D2 receptor agonists and antagonists Psychopharmacology 235:1427-1437 doi:10.1007/s00213-018-4851-6
Sparks LM, Sciascia JM, Ayorech Z, Chaudhri N (2014) Vendor differences in alcohol consumption and the contribution of dopamine receptors to pavlovian-conditioned alcohol-seeking in Long-Evans rats Psychopharmacology 231:753-764 doi:10.1007/s00213-013-3292-5
Srey CS, Maddux J-MN, Chaudhri N (2015) The attribution of incentive salience to Pavlovian alcohol cues: a shift from goal-tracking to sign-tracking Frontiers in Behavioral Neuroscience 9:54 doi:10.3389/fnbeh.2015.00054
Stringfield SJ, Madayag AC, Boettiger CA, Robinson DL (2019) Sex differences in nicotine-enhanced Pavlovian conditioned approach in rats Biology of Sex Differences 10:37 doi:10.1186/s13293-019-0244-8
Villaruel FR, Chaudhri N (2016) Individual differences in the attribution of incentive salience to a Pavlovian alcohol cue Frontiers in Behavioral Neuroscience 10 doi:10.3389/fnbeh.2016.00238
Wyvell CL, Berridge KC (2000) Intra-accumbens amphetamine increases the conditioned incentive salience of sucrose reward: Enhancement of reward “wanting” without enhanced “liking” or response reinforcement The Journal of Neuroscience 20:8122-8130 doi:10.1523/jneurosci.20-21-08122.2000
Wyvell CL, Berridge KC (2001) Incentive sensitization by previous amphetamine exposure: Increased cue-triggered “wanting” for sucrose reward The Journal of Neuroscience 21:7831-7840 doi:10.1523/JNEUROSCI.21-19-07831.2001
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