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Differential contributions of dopamine and serotonin to orbitofrontal cortex function in the marmoset.

Walker SC, Robbins TW, Roberts AC - Cereb. Cortex (2008)

Bottom Line: OFC and dopamine are involved in the process by which neutral stimuli take on reinforcing properties, by virtue of their prior association with reward, and guide behavior.Thus, we compared the performance of marmosets with dopaminergic or serotoninergic OFC depletions on a test of conditioned reinforcement.In contrast, monkeys with dopamine depletion were insensitive to conditioned reinforcers and displayed persistent responding in the absence of reward in extinction, a pattern of deficits that may reflect basic deficits in the associative processing of reward.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Psychology, University of Cambridge, UK.

ABSTRACT
We have shown previously that the inhibitory control functions of the orbitofrontal cortex (OFC) are disrupted by serotonin, but not dopamine depletions. However, both dopamine and serotonin terminals and receptors are present within the OFC and thus the aim of the present study was to determine the differential contributions of these neurotransmitters to orbitofrontal function. OFC and dopamine are involved in the process by which neutral stimuli take on reinforcing properties, by virtue of their prior association with reward, and guide behavior. Thus, we compared the performance of marmosets with dopaminergic or serotoninergic OFC depletions on a test of conditioned reinforcement. To further our understanding of serotonin in behavioral flexibility, the effect of these depletions was also compared on the extinction of a visual discrimination. Monkeys with serotonin depletions of the OFC displayed stimulus-bound responding on both tests of conditioned reinforcement and discrimination extinction suggesting that orbitofrontal serotonin plays a specific role in preventing competing, task irrelevant, salient stimuli from biasing responding. In contrast, monkeys with dopamine depletion were insensitive to conditioned reinforcers and displayed persistent responding in the absence of reward in extinction, a pattern of deficits that may reflect basic deficits in the associative processing of reward.

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(a) Mean trials to extinction (±SEM) for control (n = 4), DA-depleted (n = 4), and 5-HT (n = 4) depleted monkeys. *DA-depleted monkeys took significantly more trials to extinguish responding than control or 5-HT depleted monkeys, P < 0.01. (b) Proportion of responses in extinction which were classified as perseverative (individual data represented by the filled shapes). *5-HT depleted monkeys made a significantly higher proportion of perseverative responses to the previously rewarded stimulus than DA-depleted monkeys, P < 0.01.
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fig4: (a) Mean trials to extinction (±SEM) for control (n = 4), DA-depleted (n = 4), and 5-HT (n = 4) depleted monkeys. *DA-depleted monkeys took significantly more trials to extinguish responding than control or 5-HT depleted monkeys, P < 0.01. (b) Proportion of responses in extinction which were classified as perseverative (individual data represented by the filled shapes). *5-HT depleted monkeys made a significantly higher proportion of perseverative responses to the previously rewarded stimulus than DA-depleted monkeys, P < 0.01.

Mentions: Figure 4a shows that DA-depleted monkeys continued to respond for significantly longer than control or 5-HT depleted monkeys following removal of the primary reward. One-way ANOVA revealed that there was a significant difference between groups in the number of trials before responding was extinguished (F2,9 = 47.98, P < 0.01). Post hoc analysis using Fisher's Least Significance Difference (LSD) showed that DA-depleted monkeys responded for significantly more trials than either control or 5-HT depleted monkeys (P's < 0.01), with controls and 5-HT depleted monkeys not differing from each other. However, although 5-HT depleted monkeys extinguished as quickly as controls, their overall pattern of responding differed. Figure 4b shows the mean proportion of trials completed by each group in which responding had been perseverative. 5-HT depleted monkeys tended to show a far higher proportion of perseverative responses than DA depleted or control monkeys. A one-way ANOVA revealed that there was a significant difference between groups (F2,9 = 6.29, P < 0.02). Post hoc analysis using Tukey's LSD showed that the difference between 5-HT and DA-depleted groups was significantly different (P < 0.01) but the difference between 5-HT depleted and control monkeys was not (P = 0.1). The latter was due primarily to one control monkey extinguishing responding very rapidly, before sampling the previously unrewarded stimulus.


Differential contributions of dopamine and serotonin to orbitofrontal cortex function in the marmoset.

Walker SC, Robbins TW, Roberts AC - Cereb. Cortex (2008)

(a) Mean trials to extinction (±SEM) for control (n = 4), DA-depleted (n = 4), and 5-HT (n = 4) depleted monkeys. *DA-depleted monkeys took significantly more trials to extinguish responding than control or 5-HT depleted monkeys, P < 0.01. (b) Proportion of responses in extinction which were classified as perseverative (individual data represented by the filled shapes). *5-HT depleted monkeys made a significantly higher proportion of perseverative responses to the previously rewarded stimulus than DA-depleted monkeys, P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651474&req=5

fig4: (a) Mean trials to extinction (±SEM) for control (n = 4), DA-depleted (n = 4), and 5-HT (n = 4) depleted monkeys. *DA-depleted monkeys took significantly more trials to extinguish responding than control or 5-HT depleted monkeys, P < 0.01. (b) Proportion of responses in extinction which were classified as perseverative (individual data represented by the filled shapes). *5-HT depleted monkeys made a significantly higher proportion of perseverative responses to the previously rewarded stimulus than DA-depleted monkeys, P < 0.01.
Mentions: Figure 4a shows that DA-depleted monkeys continued to respond for significantly longer than control or 5-HT depleted monkeys following removal of the primary reward. One-way ANOVA revealed that there was a significant difference between groups in the number of trials before responding was extinguished (F2,9 = 47.98, P < 0.01). Post hoc analysis using Fisher's Least Significance Difference (LSD) showed that DA-depleted monkeys responded for significantly more trials than either control or 5-HT depleted monkeys (P's < 0.01), with controls and 5-HT depleted monkeys not differing from each other. However, although 5-HT depleted monkeys extinguished as quickly as controls, their overall pattern of responding differed. Figure 4b shows the mean proportion of trials completed by each group in which responding had been perseverative. 5-HT depleted monkeys tended to show a far higher proportion of perseverative responses than DA depleted or control monkeys. A one-way ANOVA revealed that there was a significant difference between groups (F2,9 = 6.29, P < 0.02). Post hoc analysis using Tukey's LSD showed that the difference between 5-HT and DA-depleted groups was significantly different (P < 0.01) but the difference between 5-HT depleted and control monkeys was not (P = 0.1). The latter was due primarily to one control monkey extinguishing responding very rapidly, before sampling the previously unrewarded stimulus.

Bottom Line: OFC and dopamine are involved in the process by which neutral stimuli take on reinforcing properties, by virtue of their prior association with reward, and guide behavior.Thus, we compared the performance of marmosets with dopaminergic or serotoninergic OFC depletions on a test of conditioned reinforcement.In contrast, monkeys with dopamine depletion were insensitive to conditioned reinforcers and displayed persistent responding in the absence of reward in extinction, a pattern of deficits that may reflect basic deficits in the associative processing of reward.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Psychology, University of Cambridge, UK.

ABSTRACT
We have shown previously that the inhibitory control functions of the orbitofrontal cortex (OFC) are disrupted by serotonin, but not dopamine depletions. However, both dopamine and serotonin terminals and receptors are present within the OFC and thus the aim of the present study was to determine the differential contributions of these neurotransmitters to orbitofrontal function. OFC and dopamine are involved in the process by which neutral stimuli take on reinforcing properties, by virtue of their prior association with reward, and guide behavior. Thus, we compared the performance of marmosets with dopaminergic or serotoninergic OFC depletions on a test of conditioned reinforcement. To further our understanding of serotonin in behavioral flexibility, the effect of these depletions was also compared on the extinction of a visual discrimination. Monkeys with serotonin depletions of the OFC displayed stimulus-bound responding on both tests of conditioned reinforcement and discrimination extinction suggesting that orbitofrontal serotonin plays a specific role in preventing competing, task irrelevant, salient stimuli from biasing responding. In contrast, monkeys with dopamine depletion were insensitive to conditioned reinforcers and displayed persistent responding in the absence of reward in extinction, a pattern of deficits that may reflect basic deficits in the associative processing of reward.

Show MeSH
Related in: MedlinePlus