Dopamine in the orbitofrontal cortex regulates operant responding under a progressive ratio of reinforcement in rats

Prefrontocortical dopamine (DA) plays an essential role in the regulation of cognitive functions and behavior. The orbitofrontal cortex (OFC) receives a dopaminergic projection from the ventral tegmental area and is particularly important for goal-directed appetitive behaviors and for the neural representation of reward value. We here examined the effects of DA receptor blockers locally infused into the OFC, on instrumental behavior under a progressive schedule of reinforcement. After continuous reinforcement training (lever pressing for casein pellets) rats received bilateral intra-OFC-infusions of the DA D1-receptor antagonist SCH23390 (3 microg/0.5 microl), the DA D2-receptor antagonist sulpiride (3 microg/0.5 microl), or phosphate buffered saline through chronically indwelling cannulae. Immediately after infusion they were tested under a time-constrained progressive ratio schedule of reinforcement (3, 6, 9, 12, ... lever presses for 1 casein pellet within 180 s). Both SCH23390 and sulpiride led to a significant reduction of the break point (cessation to respond to the increasing criterion of instrumental effort) compared to vehicle infusions. A food preference test revealed no drug effects on the amount of consumed pellets and on the preference of casein pellets over laboratory chow. Leftward shifts of the break point in progressive ratio tasks indicate a disturbance of the mechanisms that translate motivation into appetitive behavior under conditions of increasing instrumental effort. Therefore, our data indicate that orbitofrontal dopamine is necessary for reward-related instrumental behavior.

[1]  J. Price,et al.  The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. , 2000, Cerebral cortex.

[2]  G. Schoenbaum,et al.  Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning , 1998, Nature Neuroscience.

[3]  V Bassareo,et al.  Differential Influence of Associative and Nonassociative Learning Mechanisms on the Responsiveness of Prefrontal and Accumbal Dopamine Transmission to Food Stimuli in Rats Fed Ad Libitum , 1997, The Journal of Neuroscience.

[4]  J. Hollerman,et al.  Reward processing in primate orbitofrontal cortex and basal ganglia. , 2000, Cerebral cortex.

[5]  Wolfgang Hauber,et al.  Orbital prefrontal cortex and guidance of instrumental behaviour in rats under reversal conditions , 2003, Behavioural Brain Research.

[6]  R. Richardson,et al.  Dopamine Antagonists in the Orbital Prefrontal Cortex Reduce Prepulse Inhibition of the Acoustic Startle Reflex in the Rat , 1999, Pharmacology Biochemistry and Behavior.

[7]  G. Schoenbaum,et al.  Encoding Predicted Outcome and Acquired Value in Orbitofrontal Cortex during Cue Sampling Depends upon Input from Basolateral Amygdala , 2003, Neuron.

[8]  M. Ho,et al.  Effects of 8-OH-DPAT and WAY-100635 on performance on a time-constrained progressive-ratio schedule , 2003, Psychopharmacology.

[9]  G. Schoenbaum,et al.  Orbitofrontal Cortex and Representation of Incentive Value in Associative Learning , 1999, The Journal of Neuroscience.

[10]  Mitsuo Nakamura,et al.  Neural systems for behavioral activation and reward , 1999, Current Opinion in Neurobiology.

[11]  C. M. Bradshaw,et al.  Comparison of the effects of clozapine, haloperidol, chlorpromazine and d-amphetamine on performance on a time-constrained progressive ratio schedule and on locomotor behaviour in the rat , 2000, Psychopharmacology.

[12]  J. Salamone,et al.  Behavioral functions of nucleus accumbens dopamine: Empirical and conceptual problems with the anhedonia hypothesis , 1997, Neuroscience & Biobehavioral Reviews.

[13]  T. Robbins,et al.  THE FUNCTIONAL ROLE OF MESOTELENCEPHALIC DOPAMINE SYSTEMS , 1992, Biological reviews of the Cambridge Philosophical Society.

[14]  M. Koch,et al.  Role of nucleus accumbens dopamine D1 and D2 receptors in instrumental and Pavlovian paradigms of conditioned reward , 2000, Psychopharmacology.

[15]  Geoffrey Schoenbaum,et al.  A systems approach to orbitofrontal cortex function: recordings in rat orbitofrontal cortex reveal interactions with different learning systems , 2003, Behavioural Brain Research.

[16]  B. Berger,et al.  Dopaminergic innervation of the cerebral cortex: unexpected differences between rodents and primates , 1991, Trends in Neurosciences.

[17]  J. Fuster.  Frontal lobe and cognitive development , 2002, Journal of neurocytology.

[18]  J. O'Doherty,et al.  Encoding Predictive Reward Value in Human Amygdala and Orbitofrontal Cortex , 2003, Science.

[19]  T. Tzschentke.  Pharmacology and behavioral pharmacology of the mesocortical dopamine system , 2001, Progress in Neurobiology.

[20]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[21]  E. Rolls.  The orbitofrontal cortex and reward. , 2000, Cerebral cortex.

[22]  T. Robbins,et al.  Chemical neuromodulation of frontal-executive functions in humans and other animals , 2000, Experimental Brain Research.

[23]  J. Deakin,et al.  Effects of orbital prefrontal cortex dopamine depletion on inter-temporal choice: a quantitative analysis , 2004, Psychopharmacology.

[24]  W HODOS,et al.  Progressive Ratio as a Measure of Reward Strength , 1961, Science.