Elsevier

Neuroscience

Volume 154, Issue 4, 17 July 2008, Pages 1195-1204
Neuroscience

Behavioural neuroscience
Guidance of instrumental behavior under reversal conditions requires dopamine D1 and D2 receptor activation in the orbitofrontal cortex

https://doi.org/10.1016/j.neuroscience.2008.04.046Get rights and content

Abstract

The orbitofrontal cortex (OFC) plays a critical role in learning a reversal of stimulus–reward contingencies. Dopamine (DA) neurons probably support reversal learning by emitting prediction error signals that indicate the discrepancy between the actually received reward and its prediction. However, the role of DA receptor-mediated signaling in the OFC to adapt behavior to changing stimulus–reward contingencies is largely unknown. Here we examined the effects of a selective D1 or D2 receptor blockade in the OFC on learning a reversal of previously acquired stimulus–reward magnitude contingencies. Rats were trained on a reaction time (RT) task demanding conditioned lever release with discriminative visual stimuli signaling in advance the upcoming reward magnitude (one or five food pellets). After acquisition, RTs were guided by stimulus-associated reward magnitudes, i.e. RTs of responses were significantly shorter for expected high versus low reward. Thereafter, stimulus–reward magnitude contingencies were reversed and learning was tested under reversal conditions for three blocks after pre-trial infusions of the selective D1 or D2 receptor antagonists R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepinhydrochloride (SCH23390), eticlopride, or vehicle. For comparisons, we included intra-OFC infusions of the selective N-methyl-d-aspartate receptor antagonist AP5. Results revealed that in animals subjected to intra-OFC infusions of SCH23390 or eticlopride learning a reversal of previously acquired stimulus reward-magnitude contingencies was impaired. Thus, in a visual discrimination task as used here, D1 and D2 receptor-mediated signaling in the OFC seems to be necessary to update the reward-predictive significance of stimuli.

Section snippets

Animals

Eighty-four Lister-Hooded rats (Harlan-Winkelmann, Borchen, Germany) were housed in transparent plastic cages (55×39×27 cm, Ferplast, Nürnberg, Germany). Temperature (20±2 °C) and humidity (50–60%) in the animal house were kept constant and a 12-h light/dark schedule was used with lights on between 7:00 h and 19:00 h. Rats were given ad libitum access to water; food was restricted to 15 g per animal and day. On days without behavioral testing, rats received 15 g standard laboratory maintenance

Results

According to their performance during acquisition, animals in experiments 1–3 were divided in two groups to be treated with vehicle or drug during reversal. The groups were chosen that no significant difference of RT was detectable during acquisition (F<1).

Discussion

The present study demonstrates dissociable effects of a D1 and D2 receptor blockade versus an NMDA receptor blockade in the OFC on adapting instrumental behavior to changing stimulus–reward contingencies. A blockade of intra-OFC D1 or D2 receptors during reversal did not alter the number of early responses, but slowed learning to discriminate the current stimulus–reward magnitude contingencies. As previously shown (Bohn et al., 2003a), blockade of intra-OFC NMDA receptor increased the number of

Acknowledgments

This research was supported by the DFG (Ha2340/8-1).

References (65)

  • J. O'Doherty

    Can't learn without you: predictive value coding in orbitofrontal cortex requires the basolateral amygdala

    Neuron

    (2003)
  • M.E. Rice et al.

    Diffusion coefficients of neurotransmitters and their metabolites in brain extracellular fluid space

    Neuroscience

    (1985)
  • R.M. Ridley et al.

    An analysis of visual object reversal learning in the marmoset after amphetamine and haloperidol

    Pharmacol Biochem Behav

    (1981)
  • T.A. Stalnaker et al.

    Basolateral amygdala lesions abolish orbitofrontal-dependent reversal impairments

    Neuron

    (2007)
  • K. Taghzouti et al.

    Alternation behavior, spatial discrimination, and reversal disturbances following 6-hydroxydopamine lesions in the nucleus accumbens of the rat

    Behav Neural Biol

    (1985)
  • A.E. Baldwin et al.

    Appetitive instrumental learning requires coincident activation of NMDA and dopamine D1 receptors within the medial prefrontal cortex

    J Neurosci

    (2002)
  • J.M. Birrell et al.

    Medial frontal cortex mediates perceptual attentional set shifting in the rat

    J Neurosci

    (2000)
  • I. Bohn et al.

    NMDA receptors in the rat orbital prefrontal cortex are involved in guidance of instrumental behaviour under reversal conditions

    Cereb Cortex

    (2003)
  • I. Bohn et al.

    Orbital prefrontal cortex and guidance of instrumental behavior of rats by visuospatial stimuli predicting reward magnitude

    Learn Mem

    (2003)
  • P.J. Brasted et al.

    Unilateral lesions of the dorsal striatum in rats disrupt responding in egocentric space

    J Neurosci

    (1997)
  • C. Calaminus et al.

    Intact discrimination reversal learning but slowed responding to reward-predictive cues after dopamine D1 and D2 receptor blockade in the nucleus accumbens of rats

    Psychopharmacology (Berl)

    (2006)
  • N. Capriles et al.

    A role for the prefrontal cortex in stress- and cocaine-induced reinstatement of cocaine seeking in rats

    Psychopharmacology (Berl)

    (2003)
  • Y. Chudasama et al.

    Rhesus monkeys with orbital prefrontal cortex lesions can learn to inhibit prepotent responses in the reversed reward contingency task

    Cereb Cortex

    (2007)
  • Y. Chudasama et al.

    Dissociable contributions of the orbitofrontal and infralimbic cortex to pavlovian autoshaping and discrimination reversal learning: further evidence for the functional heterogeneity of the rodent frontal cortex

    J Neurosci

    (2003)
  • H.F. Clarke et al.

    Cognitive inflexibility after prefrontal serotonin depletion is behaviorally and neurochemically specific

    Cereb Cortex

    (2007)
  • P. Collins et al.

    The effect of dopamine depletion from the caudate nucleus of the common marmoset (Callithrix jacchus) on tests of prefrontal cognitive function

    Behav Neurosci

    (2000)
  • R. Cools et al.

    Defining the neural mechanisms of probabilistic reversal learning using event-related functional magnetic resonance imaging

    J Neurosci

    (2002)
  • H.D. Critchley et al.

    Hunger and satiety modify the responses of olfactory and visual neurons in the primate orbitofrontal cortex

    J Neurophysiol

    (1996)
  • R. Dias et al.

    Primate analogue of the Wisconsin Card Sorting Test: effects of excitotoxic lesions of the prefrontal cortex in the marmoset

    Behav Neurosci

    (1996)
  • A.T. Ferry et al.

    Effects of excitotoxic lesions in the ventral striatopallidal-thalamocortical pathway on odor reversal learning: inability to extinguish an incorrect response

    Exp Brain Res

    (2000)
  • S.B. Floresco et al.

    Multiple dopamine receptor subtypes in the medial prefrontal cortex of the rat regulate set-shifting

    Neuropsychopharmacology

    (2006)
  • M.J. Frank et al.

    Anatomy of a decision: striato-orbitofrontal interactions in reinforcement learning, decision making, and reversal

    Psychol Rev

    (2006)

    • Cited by (22)

    • Cognitive impairment and gene expression alterations in a rodent model of binge eating disorder

      2017, Physiology and Behavior
      Citation Excerpt :

      We also found BEP specific reductions in the expression of Drd1 and Drd4 in the OFC region as compared to the CON group. Although, dopamine (DA) depletion in the OFC of marmoset monkeys did not produce any reversal learning deficits [98], and we did not find any correlations between cortical dopamine receptors and performance on cognitive tasks, there are evidences from both rodent and human studies linking D1 receptor modulation in the PFC to impairments in cognitive flexibility or spatial working memory [106–111], and to increased palatable food intake [112–114]. Likewise, several clinical studies have implicated that DRD4 gene polymorphisms are associated with executive dysfunction [115–117] as well as palatable food craving, fat intake, and binge eating behavior [118–120].

    • Brief social isolation in early adolescence affects reversal learning and forebrain BDNF expression in adult rats

      2011, Brain Research Bulletin
      Citation Excerpt :

      Successful reversal learning performance depends on the normal function of the mPFC [19,39,47], as well as several sub-cortical forebrain regions, such as the striatum and nucleus accumbens [3,12,34,43]. The flexibility-mediating brain circuit engages a variety of neurotransmitter systems, such as dopamine and glutamate [2,47]. Both dopaminergic and glutamatergic systems mature during adolescence [42], which is a process that is supported by neurotrophic factor systems.

    • A role for dopamine D2 receptors in reversal learning

      2009, Neuroscience

    • The dopamine D<inf>3</inf> receptor antagonist, S33138, counters cognitive impairment in a range of rodent and primate procedures

      2010, International Journal of Neuropsychopharmacology

    • NMDA and D2-like receptors modulate cognitive flexibility in a color discrimination reversal task in pigeons

      2010, Behavioral Neuroscience

    • Categories of Novelty and States of Uncertainty

      2009, Review of General Psychology
    View all citing articles on Scopus
    View full text
    Copyright © 2008 IBRO. Published by Elsevier Ltd. All rights reserved.