DRUGS OF ABUSE, REWARD COMPARISON, AND THE THALAMUS

Summary

Principal Investigator: PATRICIA GRIGSON
Abstract: Rats avoid intake of a saccharin conditioned stimulus (CS) when paired with a drug of abuse (LeMagnen, 1969;for reviews, see Gamzu, Vincent, &Boff, 1985;Goudie, 1987;Hunt &Amit, 1987). For decades, the suppressive effects of drugs of abuse on CS intake have been attributed to presumed aversive drug properties (Lester, Nachman, &LeMagnen, 1970). Data gleaned over the past decade, however, have provided substantive support for the hypothesis that rats avoid intake of the taste cue because the tastant is devalued in anticipation of the availability of the highly rewarding properties of the abused substance (Grigson, 1997;for review, see Grigson et al., 2008;Grigson, in press). As such, the present model serves as a unique model for the systematic study of drug-induced devaluation of natural rewards. New data, however, suggest that there may be a second process contributing to devaluation of the taste cue and this process includes an element of aversion (Wheeler et al., 2008). We hypothesize, then, that there are two processes: Devaluation of the taste cue by the highly rewarding drug properties and devaluation of the taste cue as it becomes associated with craving and withdrawal in anticipation of the impending availability of drug. The goal here is to identify the underlying circuitry. Lesion data collected over the last funding period clearly demonstrate an essential role for the gustatory thalamocortical loop (Schroy et al., 2005;Geddes et al., 2008;Geddes et al., in preparation). Even so, there is some indication that the disruptive effect of lesions of this pathway may be overridden by the use of higher doses of the drugs. Specific Aim 1A, 1B, and 1C will test the hypothesis that disconnection of the gustatory thalamocortical loop will disrupt the suppressive effects of low and high concentrations/doses of sweets and drugs, but not those of the illness-inducing agent, LiCl. Recent microdialysis data show that dopamine in the NAc tracks morphine-induced devaluation of the saccharin cue when morphine is administered by the experimenter (Grigson &Hajnal, 2007). Specific Aim 2A will use central lesions and microdialysis to test the hypothesis that the NAc depends upon an intact gustatory thalamocortical loop to track devaluation induced by self-administered cocaine. The present set of studies can be completed in 2 years. The results will: (a) Verify that an intact gustatory thalamocoritical loop is essential for devaluation induced by 'self-administered'sweets and drug;(b) Demonstrate that the disruptive effect of this lesion is retained even when using higher concentrations/ doses of rewarding sweets and drugs (i.e., cocaine and heroin);and (c) Reveal that the nucleus accumbens depends upon an intact thalamocoritical loop to track cocaine's devaluation of a sweet.
Funding Period: ----------------2000 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Lewis rats are more sensitive than Fischer rats to successive negative contrast, but less sensitive to the anxiolytic and appetite-stimulating effects of chlordiazepoxide
    Christopher S Freet
    The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Pharmacol Biochem Behav 85:378-84. 2006
  2. pmc A drug-paired taste cue elicits withdrawal and predicts cocaine self-administration
    Jennifer E Nyland
    The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States
    Behav Brain Res 240:87-90. 2013
  3. pmc Bilateral lesions of the thalamic trigeminal orosensory area dissociate natural from drug reward in contrast paradigms
    Jennifer E Nyland
    Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Behav Neurosci 126:538-50. 2012
  4. pmc Variable effects of parabrachial nucleus lesions on salt appetite in rats depending upon experimental paradigm and saline concentration
    Edward M Stricker
    Department of Neuroscience, 210 Langley Hall, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Behav Neurosci 127:275-84. 2013
  5. pmc The state of the reward comparison hypothesis: theoretical comment on Huang and Hsiao (2008)
    Patricia Sue Grigson
    Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Behav Neurosci 122:1383-90. 2008
  6. pmc Gustatory insular cortex lesions disrupt drug-induced, but not lithium chloride-induced, suppression of conditioned stimulus intake
    RASTAFA I GEDDES
    Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA 17033, USA
    Behav Neurosci 122:1038-50. 2008
  7. pmc Abnormal latent inhibition and impulsivity in coloboma mice, a model of ADHD
    Kristy J Bruno
    Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Neurobiol Dis 25:206-16. 2007
  8. ncbi Heroin self-administration: II. CNS gene expression following withdrawal and cue-induced drug-seeking behavior
    KARA L KUNTZ
    Department of Pharmacology, Pennsylvania State University College of Medicine, R130, 500 University Drive, Hershey, PA 17033, USA
    Pharmacol Biochem Behav 90:349-56. 2008
  9. ncbi Behavioral and electrophysiological indices of negative affect predict cocaine self-administration
    Robert A Wheeler
    Department of Psychology, University of North Carolina, Chapel Hill, NC 27599, USA
    Neuron 57:774-85. 2008
  10. ncbi Once is too much: conditioned changes in accumbens dopamine following a single saccharin-morphine pairing
    Patricia Sue Grigson
    Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Behav Neurosci 121:1234-42. 2007

Scientific Experts

  • Nu Chu Liang
  • Chuang Liu
  • Kara L Kuntz-Melcavage
  • Patricia S Grigson
  • Jennifer E Nyland
  • Patricia Sue Grigson
  • Christopher S Freet
  • Edward M Stricker
  • Ralph Norgren
  • Robert A Wheeler
  • KARA L KUNTZ
  • RASTAFA I GEDDES
  • Robert C Twining
  • Kristy J Bruno
  • Danielle N Alexander
  • Kruti M Patel
  • Kent E Vrana
  • JOSHUA L JONES
  • Li Han
  • Willard M Freeman
  • Anne E Baldwin
  • Regina M Carelli
  • Jennifer M Slater
  • Kiyoshi Egami
  • Ellen J Hess
  • Andras Hajnal
  • Jason D Tesche
  • Dennie M Tompers
  • Katherine E Riegel

Detail Information

Publications16

  1. pmc Lewis rats are more sensitive than Fischer rats to successive negative contrast, but less sensitive to the anxiolytic and appetite-stimulating effects of chlordiazepoxide
    Christopher S Freet
    The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Pharmacol Biochem Behav 85:378-84. 2006
    ..Together, the results show that, while both Lewis and Fischer rats demonstrate SNC, the effect is more sustained in the Lewis rats and these rats are insensitive to both the anxiolytic and the appetite-stimulating effects of CDP...
  2. pmc A drug-paired taste cue elicits withdrawal and predicts cocaine self-administration
    Jennifer E Nyland
    The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States
    Behav Brain Res 240:87-90. 2013
    ..v.). The results show that presentation of a morphine- or cocaine-paired taste cue is sufficient to elicit naloxone-induced withdrawal symptoms, and greater withdrawal predicts greater cocaine self-administration in rats...
  3. pmc Bilateral lesions of the thalamic trigeminal orosensory area dissociate natural from drug reward in contrast paradigms
    Jennifer E Nyland
    Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Behav Neurosci 126:538-50. 2012
    ..As such, this is the first manipulation found to dissociate avoidance of a taste cue when mediated by a sweet or by a drug of abuse...
  4. pmc Variable effects of parabrachial nucleus lesions on salt appetite in rats depending upon experimental paradigm and saline concentration
    Edward M Stricker
    Department of Neuroscience, 210 Langley Hall, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Behav Neurosci 127:275-84. 2013
    ..These and other observations indicate that lesions of the gustatory PBN in rats may or may not eliminate salt appetite, depending on which model is used and which concentration of NaCl solution is available...
  5. pmc The state of the reward comparison hypothesis: theoretical comment on Huang and Hsiao (2008)
    Patricia Sue Grigson
    Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Behav Neurosci 122:1383-90. 2008
    ..This commentary addresses the current state of the reward comparison hypothesis in the context of the experiments completed by Huang and Hsiao and their new task-dependent drug effects hypothesis...
  6. pmc Gustatory insular cortex lesions disrupt drug-induced, but not lithium chloride-induced, suppression of conditioned stimulus intake
    RASTAFA I GEDDES
    Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA 17033, USA
    Behav Neurosci 122:1038-50. 2008
    ..Finally, these same cortical lesions had no impact on LiCl-induced conditioned taste aversion. The current data show that the insular taste cortex plays an integral role in drug-induced avoidance of a gustatory CS...
  7. pmc Abnormal latent inhibition and impulsivity in coloboma mice, a model of ADHD
    Kristy J Bruno
    Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Neurobiol Dis 25:206-16. 2007
    ..In summary, coloboma mice exhibit hyperactivity, inattention as determined by latent inhibition, and impulsivity, and norepinephrine mediates hyperactivity and inattention but not impulsivity in these mice...
  8. ncbi Heroin self-administration: II. CNS gene expression following withdrawal and cue-induced drug-seeking behavior
    KARA L KUNTZ
    Department of Pharmacology, Pennsylvania State University College of Medicine, R130, 500 University Drive, Hershey, PA 17033, USA
    Pharmacol Biochem Behav 90:349-56. 2008
    ..These latter observations of persistent changes in gene expression following abstinence may reflect molecular correlates of relapse liability...
  9. ncbi Behavioral and electrophysiological indices of negative affect predict cocaine self-administration
    Robert A Wheeler
    Department of Psychology, University of North Carolina, Chapel Hill, NC 27599, USA
    Neuron 57:774-85. 2008
    ..The dynamic nature of this conditioned switch in affect and the neural code reveals a mechanism by which cues may exert control over drug self-administration...
  10. ncbi Once is too much: conditioned changes in accumbens dopamine following a single saccharin-morphine pairing
    Patricia Sue Grigson
    Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Behav Neurosci 121:1234-42. 2007
    ..Reward comparison effects, then, are cross-modal, bidirectional, and immediate, resulting in both unconditioned and conditioned changes in brain and behavior...
  11. pmc Pontine and thalamic influences on fluid rewards: I. Operant responding for sucrose and corn oil
    Nu Chu Liang
    Department of Neural and Behavioral Sciences, College of Medicine, The Pennsylvania State University, Hershey, PA 17033, USA
    Physiol Behav 105:576-88. 2012
    ..Together, the data imply that the PBN but not the TOA is critical for the perception of, or responding to the reward value of sucrose and corn oil...
  12. pmc Pontine and thalamic influences on fluid rewards: III. Anticipatory contrast for sucrose and corn oil
    Nu Chu Liang
    Department of Neural and Behavioral Sciences, College of Medicine, The Pennsylvania State University, Hershey, PA 17033, USA
    Physiol Behav 105:595-606. 2012
    ..Although the sensory modalities needed for the oral detection of fats remain controversial, it appears that the PBN is involved in processing the comparison of disparate concentrations of sucrose and oil reward...
  13. pmc Pontine and thalamic influences on fluid rewards: II. Sucrose and corn oil conditioned aversions
    Nu Chu Liang
    Department of Neural and Behavioral Sciences, College of Medicine, The Pennsylvania State University, Hershey, PA 17033, USA
    Physiol Behav 105:589-94. 2012
    ....
  14. pmc Ethanol-induced conditioned taste avoidance: reward or aversion?
    Chuang Liu
    Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Alcohol Clin Exp Res 33:522-30. 2009
    ....
  15. pmc Gene expression changes following extinction testing in a heroin behavioral incubation model
    Kara L Kuntz-Melcavage
    Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA, USA
    BMC Neurosci 10:95. 2009
    ..Extinction sessions were conducted on groups after either 1 d or 14 d of drug-free enforced abstinence to demonstrate behavioral incubation...