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A cocaine cue is more preferred and evokes more frequency-modulated 50-kHz ultrasonic vocalizations in rats prone to attribute incentive salience to a food cue

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Abstract

Rationale

Individuals vary considerably in the extent to which they attribute incentive salience to food-associated cues.

Objectives

We asked whether individuals prone to attribute incentive salience to a food cue are also prone to attribute incentive properties to a stimulus associated with a drug of abuse—cocaine.

Methods

We first identified those rats that attributed incentive salience to a food cue by quantifying the extent to which they came to approach and engage a food cue. We then used a conditioned place preference procedure to pair an injection of 10 mg/kg cocaine (i.p.) with one distinct floor texture (grid or holes) and saline with another. Following 8 days of conditioning, each rat was given a saline injection and placed into a chamber that had both floors present. We measured the time spent on each floor, and also 50-kHz ultrasonic vocalizations, which have been associated with positive affective states.

Results

Rats that vigorously engaged the food cue (“sign trackers”) expressed a preference for the cocaine-paired floor compared to those that did not (“goal trackers”). In addition, sign trackers made substantially more frequency-modulated 50-kHz vocalizations when injected with cocaine and when later exposed to the cocaine cue.

Conclusions

Rats prone to attribute incentive salience to a food cue are also prone to attribute incentive motivational properties to a tactile cue associated with cocaine. We suggest that individuals prone to attribute incentive salience to reward cues will have difficulty resisting them and, therefore, may be especially vulnerable to develop impulse control disorders, including addiction.

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References

  • Ahrens AM, Ma ST, Maier EY, Duvauchelle CL, Schallert T (2009) Repeated intravenous amphetamine exposure: rapid and persistent sensitization of 50-kHz ultrasonic trill calls in rats. Behav Brain Res 197:205–209

    Article  PubMed  CAS  Google Scholar 

  • Anagnostaras SG, Schallert T, Robinson TE (2002) Memory processes governing amphetamine-induced psychomotor sensitization. Neuropsychopharmacology 26:703–715

    Article  PubMed  CAS  Google Scholar 

  • Beckmann JS, Marusich JA, Gipson CD, Bardo MT (2011) Novelty seeking, incentive salience and acquisition of cocaine self-administration in the rat. Behav Brain Res 216:159–165

    Article  PubMed  CAS  Google Scholar 

  • Berridge KC, Robinson TE (2003) Parsing reward. Trends Neurosci 26:507–513

    Article  PubMed  CAS  Google Scholar 

  • Bialy M, Rydz M, Kaczmarek L (2000) Precontact 50-kHz vocalizations in male rats during acquisition of sexual experience. Behav Neurosci 114:983–990

    Article  PubMed  CAS  Google Scholar 

  • Bindra D (1978) How adaptive behavior is produced: a perceptual-motivation alternative to response reinforcement. Behav Brain Res 1:41–91

    Article  Google Scholar 

  • Boakes R (1977) Performance on learning to associate a stimulus with positive reinforcement. In: Davis H, Hurwitz H (eds) Operant-Pavlovian interactions. Lawrence Erlbaum Associates, Hillsdale, pp 67–97

    Google Scholar 

  • Brown RM, Short JL, Lawrence AJ (2011) Identification of brain nuclei implicated in cocaine-primed reinstatement of conditioned place preference: a behaviour dissociable from sensitization. PLoS One 5:e15889

    Article  Google Scholar 

  • Browning JR, Browning DA, Maxwell AO, Dong Y, Jansen HT, Panksepp J, Sorg BA (2011) Positive affective vocalizations during cocaine and sucrose self-administration: a model for spontaneous drug desire in rats. Neuropharmacology 61:268–275

    Article  PubMed  CAS  Google Scholar 

  • Burgdorf J, Wood PL, Kroes RA, Moskal JR, Panksepp J (2007) Neurobiology of 50-kHz ultrasonic vocalizations in rats: electrode mapping, lesion, and pharmacology studies. Behav Brain Res 182:274–283

    Article  PubMed  Google Scholar 

  • Burgdorf J, Kroes RA, Moskal JR, Pfaus JG, Brudzynski SM, Panksepp J (2008) Ultrasonic vocalizations of rats (Rattus norvegicus) during mating, play, and aggression: behavioral concomitants, relationship to reward, and self-administration of playback. J Comp Psychol 122:357–367

    Article  PubMed  Google Scholar 

  • Burgdorf J, Panksepp J, Moskal JR (2011) Frequency-modulated 50 kHz ultrasonic vocalizations: a tool for uncovering the molecular substrates of positive affect. Neurosci Biobehav Rev. doi:10.1016/j.neubiorev.2010.11.011

  • Caggiula AR, Donny EC, White AR, Chaudhri N, Booth S, Gharib MA, Hoffman A, Perkins KA, Sved AF (2001) Cue dependency of nicotine self-administration and smoking. Pharmacol Biochem Behav 70:515–530

    Article  PubMed  CAS  Google Scholar 

  • Cardinal RN, Parkinson JA, Hall J, Everitt BJ (2002) Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex. Neurosci Biobehav Rev 26:321–352

    Article  PubMed  Google Scholar 

  • 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. Behav Brain Res 116:1–22

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Cunningham CL, Patel P (2007) Rapid induction of Pavlovian approach to an ethanol-paired visual cue in mice. Psychopharmacology (Berl) 192:231–241

    Article  CAS  Google Scholar 

  • Cunningham CL, Niehus JS, Noble D (1993) Species difference in sensitivity to ethanol's hedonic effects. Alcohol 10:97–102

    Article  PubMed  CAS  Google Scholar 

  • Cunningham CL, Tull LE, Rindal KE, Meyer PJ (2002) Distal and proximal pre-exposure to ethanol in the place conditioning task: tolerance to aversive effect, sensitization to activating effect, but no change in rewarding effect. Psychopharmacology (Berl) 160:414–424

    Article  CAS  Google Scholar 

  • Cunningham CL, Gremel CM, Groblewski PA (2006a) Drug-induced conditioned place preference and aversion in mice. Nat Protoc 1:1662–1670

    Article  PubMed  CAS  Google Scholar 

  • Cunningham CL, Patel P, Milner L (2006b) Spatial location is critical for conditioning place preference with visual but not tactile stimuli. Behav Neurosci 120:1115–1132

    Article  PubMed  Google Scholar 

  • Cunningham CL, Groblewski PA, Voorhees CM (2011) Place conditioning. In: Olmstead MC (ed) Animal models of drug addiction, neuromethods, vol 53. Humana Press, New York

    Google Scholar 

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

    Article  Google Scholar 

  • dela Cruz AM, Herin DV, Grady JJ, Cunningham KA (2009) Novel approach to data analysis in cocaine-conditioned place preference. Behav Pharmacol 20:720–730

    Article  Google Scholar 

  • Di Ciano P, Everitt BJ (2004) Conditioned reinforcing properties of stimuli paired with self-administered cocaine, heroin or sucrose: implications for the persistence of addictive behaviour. Neuropharmacology 47(Suppl 1):202–213

    Article  PubMed  Google Scholar 

  • Epstein DH, Preston KL, Stewart J, Shaham Y (2006) Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacology (Berl) 189:1–16

    Article  CAS  Google Scholar 

  • Everitt BJ, Cardinal RN, Hall G, Parkinson JA, Robbins TW (2000) Differential involvement of amygdala subsystems in appetitive conditioning and drug addiction. In: Aggleton JP (ed) The amygdala: a functional analysis. Oxford University Press, New York, pp 353–390

    Google Scholar 

  • Fidler TL, Bakner L, Cunningham CL (2004) Conditioned place aversion induced by intragastric administration of ethanol in rats. Pharmacol Biochem Behav 77:731–743

    Article  PubMed  CAS  Google Scholar 

  • 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 (Berl) 191:599–607

    Article  CAS  Google Scholar 

  • Flagel SB, Watson SJ, Akil H, Robinson TE (2008) Individual differences in the attribution of incentive salience to a reward-related cue: influence on cocaine sensitization. Behav Brain Res 186:48–56

    Article  PubMed  CAS  Google Scholar 

  • Flagel SB, Akil H, Robinson TE (2009) Individual differences in the attribution of incentive salience to reward-related cues: implications for addiction. Neuropharmacology 56(Suppl 1):139–148

    Article  PubMed  CAS  Google Scholar 

  • Flagel SB, Robinson TE, Clark JJ, Clinton SM, Watson SJ, Seeman P, Phillips PE, Akil H (2010) An animal model of genetic vulnerability to behavioral disinhibition and responsiveness to reward-related cues: implications for addiction. Neuropsychopharmacology 35:388–400

    Article  PubMed  Google Scholar 

  • Flagel SB, Clark JJ, Robinson TE, Mayo L, Czuj A, Willuhn I, Akers CA, Clinton SM, Phillips PE, Akil H (2011) A selective role for dopamine in stimulus-reward learning. Nature 469:53–57

    Article  PubMed  CAS  Google Scholar 

  • Gremel CM, Cunningham CL (2008) Roles of the nucleus accumbens and amygdala in the acquisition and expression of ethanol-conditioned behavior in mice. J Neurosci 28:1076–1084

    Article  PubMed  CAS  Google Scholar 

  • Grimm JW, Hope BT, Wise RA, Shaham Y (2001) Neuroadaptation. Incubation of cocaine craving after withdrawal. Nature 412:141–142

    Article  PubMed  CAS  Google Scholar 

  • Hearst E, Jenkins HM (1974) Sign tracking: the stimulus-reinforcer relation and directed action. Psychonomic Society, Austin

    Google Scholar 

  • Knutson B, Burgdorf J, Panksepp J (1999) High-frequency ultrasonic vocalizations index conditioned pharmacological reward in rats. Physiol Behav 66:639–643

    Article  PubMed  CAS  Google Scholar 

  • Knutson B, Burgdorf J, Panksepp J (2002) Ultrasonic vocalizations as indices of affective states in rats. Psychol Bull 128:961–977

    Article  PubMed  Google Scholar 

  • Konorski J, Miller S (1937) On two types of conditioned reflex. J Gen Psychol 16:264–272

    Article  Google Scholar 

  • Lomanowska AM, Lovic V, Rankine MJ, Mooney SJ, Robinson TE, Kraemer GW (2011) Inadequate early social experience increases the incentive salience of reward-related cues in adulthood. Behav Brain Res 220:91–99

    Article  PubMed  Google Scholar 

  • Ma ST, Maier EY, Ahrens AM, Schallert T, Duvauchelle CL (2010) Repeated intravenous cocaine experience: development and escalation of pre-drug anticipatory 50-kHz ultrasonic vocalizations in rats. Behav Brain Res 212:109–114

    Article  PubMed  CAS  Google Scholar 

  • Mahler SV, de Wit H (2010) Cue-reactors: individual differences in cue-induced craving after food or smoking abstinence. PLoS One 5:e15475

    Article  PubMed  Google Scholar 

  • Maier EY, Ahrens AM, Ma ST, Schallert T, Duvauchelle CL (2010) Cocaine deprivation effect: cue abstinence over weekends boosts anticipatory 50-kHz ultrasonic vocalizations in rats. Behav Brain Res 214:75–79

    Article  PubMed  CAS  Google Scholar 

  • Meil WM, See RE (1996) Conditioned cued recovery of responding following prolonged withdrawal from self-administered cocaine in rats: an animal model of relapse. Behav Pharmacol 7:754–763

    PubMed  CAS  Google Scholar 

  • Milton AL, Everitt BJ (2010) The psychological and neurochemical mechanisms of drug memory reconsolidation: implications for the treatment of addiction. Eur J Neurosci 31:2308–2319

    Article  PubMed  Google Scholar 

  • Morrow JD, Maren S, Robinson TE (2011) Individual variation in the propensity to attribute incentive salience to an appetitive cue predicts the propensity to attribute motivational salience to an aversive cue. Behav Brain Res 220:238–243

    Article  PubMed  Google Scholar 

  • Palmatier MI, Evans-Martin FF, Hoffman A, Caggiula AR, Chaudhri N, Donny EC, Liu X, Booth S, Gharib M, Craven L, Sved AF (2006) Dissociating the primary reinforcing and reinforcement-enhancing effects of nicotine using a rat self-administration paradigm with concurrently available drug and environmental reinforcers. Psychopharmacology (Berl) 184:391–400

    Article  CAS  Google Scholar 

  • Panksepp J, Burgdorf J (2000) 50-kHz chirping (laughter?) in response to conditioned and unconditioned tickle-induced reward in rats: effects of social housing and genetic variables. Behav Brain Res 115:25–38

    Article  PubMed  CAS  Google Scholar 

  • Panksepp J, Burgdorf J (2003) “Laughing” rats and the evolutionary antecedents of human joy? Physiol Behav 79:533–547

    Article  PubMed  CAS  Google Scholar 

  • Panksepp J, Knutson B, Burgdorf J (2002) The role of brain emotional systems in addictions: a neuro-evolutionary perspective and new ‘self-report’ animal model. Addiction 97:459–469

    Article  PubMed  Google Scholar 

  • Pavlov IP (1927) Conditioned reflexes: an investigation of the physiological activity of the cerebral cortex. Oxford University Press, London

    Google Scholar 

  • Rescorla RA (1988) Pavlovian Conditioning—Its Not What You Think It Is. Am Psychol 43:151–160

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE, Berridge KC (2003) Addiction. Annu Rev Psychol 54:25–53

    Article  PubMed  Google Scholar 

  • Robinson TE, Flagel SB (2009) Dissociating the predictive and incentive motivational properties of reward-related cues through the study of individual differences. Biol Psychiatry 65:869–873

    Article  PubMed  Google Scholar 

  • Rowlett JK, Gibson TR, Bardo MT (1994) Dissociation of buprenorphine-induced locomotor sensitization and conditioned place preference in rats. Pharmacol Biochem Behav 49:241–245

    Article  PubMed  CAS  Google Scholar 

  • Saunders BT, Robinson TE (2010) A cocaine cue acts as an incentive stimulus in some but not others: implications for addiction. Biol Psychiatry 67:730–736

    Article  PubMed  CAS  Google Scholar 

  • Saunders BT, Robinson TE (2011) Individual variation in the motivational properties of cocaine. Neuropsychopharmacology 36(8):1668–1676

    Article  PubMed  CAS  Google Scholar 

  • Skinner BF (1935) Two types of conditioned reflex and a pseudo-type. J Gen Psychol 12:66–77

    Article  Google Scholar 

  • Stewart J, de Wit H, Eikelboom R (1984) Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychol Rev 91:251–268

    Article  PubMed  CAS  Google Scholar 

  • Tomie A, Grimes KL, Pohorecky LA (2008) Behavioral characteristics and neurobiological substrates shared by Pavlovian sign-tracking and drug abuse. Brain Res Rev 58:121–135

    Article  PubMed  CAS  Google Scholar 

  • Tzschentke TM (2007) Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol 12:227–462

    Article  PubMed  CAS  Google Scholar 

  • van der Kooy D (1987) Place conditioning: a simple and effective method for assessing the motivational properties of drugs. In: Bozarth MA (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, New York, pp 229–240

    Chapter  Google Scholar 

  • Veeneman MM, Boleij H, Broekhoven MH, Snoeren EM, Guitart Masip M, Cousijn J, Spooren W, Vanderschuren LJ (2011) Dissociable roles of mGlu5 and dopamine receptors in the rewarding and sensitizing properties of morphine and cocaine. Psychopharmacology (Berl) 214:863–876

    Article  CAS  Google Scholar 

  • Vezina P, Stewart J (1987a) Conditioned locomotion and place preference elicited by tactile cues paired exclusively with morphine in an open field. Psychopharmacology (Berl) 91:375–380

    Article  CAS  Google Scholar 

  • Vezina P, Stewart J (1987b) Morphine conditioned place preference and locomotion: the effect of confinement during training. Psychopharmacology (Berl) 93:257–260

    Article  CAS  Google Scholar 

  • Wang H, Liang S, Burgdorf J, Wess J, Yeomans J (2008) Ultrasonic vocalizations induced by sex and amphetamine in M2, M4, M5 muscarinic and D2 dopamine receptor knockout mice. PLoS One 3:e1893

    Article  PubMed  Google Scholar 

  • Weiss F, Maldonado-Vlaar CS, Parsons LH, Kerr TM, Smith DL, Ben-Shahar O (2000) Control of cocaine-seeking behavior by drug-associated stimuli in rats: effects on recovery of extinguished operant-responding and extracellular dopamine levels in amygdala and nucleus accumbens. Proc Natl Acad Sci U S A 97:4321–4326

    Article  PubMed  CAS  Google Scholar 

  • White NM, Chai SC, Hamdani S (2005) Learning the morphine conditioned cue preference: cue configuration determines effects of lesions. Pharmacol Biochem Behav 81:786–796

    Article  PubMed  CAS  Google Scholar 

  • Wright JM, Gourdon JC, Clarke PB (2010) Identification of multiple call categories within the rich repertoire of adult rat 50-kHz ultrasonic vocalizations: effects of amphetamine and social context. Psychopharmacology (Berl) 211:1–13

    Article  CAS  Google Scholar 

  • 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. J Neurosci 20:8122–8130

    PubMed  CAS  Google Scholar 

  • Wyvell CL, Berridge KC (2001) Incentive sensitization by previous amphetamine exposure: increased cue-triggered “wanting” for sucrose reward. J Neurosci 21:7831–7840

    PubMed  CAS  Google Scholar 

  • Yager LM, Robinson TE (2010) Cue-induced reinstatement of food seeking in rats that differ in their propensity to attribute incentive salience to food cues. Behav Brain Res 214:30–34

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Drs. Chris Cunningham and Carrie Ferrario for their consultations on apparatus and experimental design, as well as David Haidar, Matea Mustafaj, and Rebeca Kelley for their excellent technical support. We also thank Ben Saunders for the helpful comments on an earlier version of this article. All research was conducted in concordance with current local and national US laws. This research is supported by Grant R37 DA04294 from NIDA to TER. PJM was supported by Grant T32 DA007268.

Conflict of interest

The authors declare no financial conflicts of interest.

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  1. Department of Psychology, The University of Michigan, East Hall, 530 Church Street, Ann Arbor, MI, 48109-1109, USA

    Paul J. Meyer, Sean T. Ma & Terry E. Robinson

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  1. Paul J. Meyer
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  2. Sean T. Ma
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  3. Terry E. Robinson
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Correspondence to Terry E. Robinson.

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Paul J. Meyer and Sean T. Ma contributed equally to this work.

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Meyer, P.J., Ma, S.T. & Robinson, T.E. A cocaine cue is more preferred and evokes more frequency-modulated 50-kHz ultrasonic vocalizations in rats prone to attribute incentive salience to a food cue. Psychopharmacology 219, 999–1009 (2012). https://doi.org/10.1007/s00213-011-2429-7

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