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Abnormal modulation of reward versus punishment learning by a dopamine D2-receptor antagonist in pathological gamblers.

Janssen LK, Sescousse G, Hashemi MM, Timmer MH, ter Huurne NP, Geurts DE, Cools R - Psychopharmacology (Berl.) (2015)

Bottom Line: Moreover, pervasive theoretical accounts suggest a key role for dopamine in reversal learning.In line with previous studies, blockade of D2 receptors with sulpiride impaired reward versus punishment reversal learning in controls.By contrast, sulpiride did not have any outcome-specific effects in gamblers.

View Article: PubMed Central - PubMed

Affiliation: Donders Institute for Brain, Cognition and Behavior, Radboud University, PO Box 9101, 6500 HB, Nijmegen, The Netherlands, l.k.janssen@donders.ru.nl.

ABSTRACT

Rationale: Pathological gambling has been associated with dopamine transmission abnormalities, in particular dopamine D2-receptor deficiency, and reversal learning deficits. Moreover, pervasive theoretical accounts suggest a key role for dopamine in reversal learning. However, there is no empirical evidence for a direct link between dopamine, reversal learning and pathological gambling.

Objective: The aim of the present study is to triangulate dopamine, reversal learning, and pathological gambling.

Methods: Here, we assess the hypothesis that pathological gambling is accompanied by dopamine-related problems with learning from reward and punishment by investigating effects of the dopamine D2-receptor antagonist sulpiride (400 mg) on reward- and punishment-based reversal learning in 18 pathological gamblers and 22 healthy controls, using a placebo-controlled, double-blind, counter-balanced design.

Results: In line with previous studies, blockade of D2 receptors with sulpiride impaired reward versus punishment reversal learning in controls. By contrast, sulpiride did not have any outcome-specific effects in gamblers.

Conclusion: These data demonstrate that pathological gambling is associated with a dopamine-related anomaly in reversal learning from reward and punishment.

No MeSH data available.


Related in: MedlinePlus

The effect of sulpiride on outcome-specific error rates (i.e., mean error rates on trials following unexpected rewards—mean error rates on trials following unexpected punishment). Sulpiride significantly impairs reward versus punishment learning in controls while not altering the balance between reward and punishment learning in gamblers. Error bars represent 1 SEM; *p < 0.05, ns denotes not significant
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Fig2: The effect of sulpiride on outcome-specific error rates (i.e., mean error rates on trials following unexpected rewards—mean error rates on trials following unexpected punishment). Sulpiride significantly impairs reward versus punishment learning in controls while not altering the balance between reward and punishment learning in gamblers. Error bars represent 1 SEM; *p < 0.05, ns denotes not significant

Mentions: Figure 2 shows that sulpiride altered reward versus punishment reversal learning in controls, while not altering reversal learning in gamblers. This observation was substantiated by an ANOVA of the error rates on reversal trials (Table 2), which revealed a significant interaction of group × drug × outcome (F(1,38) = 5.288, p = 0.027). When decomposing the three-way interaction effect into two-way interaction effects for each group, we found that this was driven by a drug × outcome interaction in controls (F(1,21) = 4.768, p = 0.040). By contrast, there was no drug × outcome interaction in gamblers (F(1,17) = 1.183, p = 0.292). The drug × outcome interaction in controls was due to a significant simple main effect of drug on reward learning (F(1,21) = 5.439, p = 0.030), not punishment learning (F(1,21) = 0.523, p = 0.478). Thus, sulpiride induced a shift away from reward learning in controls, while not altering the balance between reward and punishment learning in gamblers. Under placebo there was no group × outcome interaction (F(1,38) = 0.976, p = 0.329). In addition to the outcome-specific effects of sulpiride on reversal learning, there was also an outcome-nonspecific main effect of drug on error rate (F(1,38) = 4.452, p = 0.041). This was due to sulpiride impairing performance across groups and outcomes. This raises the question whether the impairment is specific to reversal trials or extends to non-reversal trials. Supplementary analysis including the within-subjects factor trial type (reversal, non-reversal reward, and non-reversal punishment trials) revealed a significant group × drug × outcome × trial type interaction (F(2,37) = 3.581, p = 0.038). When decomposing this interaction into the simple three-way interaction effect for each trial type, we found that this four-way interaction was driven by a group × drug × outcome interaction for reversal trials only. In line with that, there was no significant effect of group, drug or outcome on performance on non-reversal trials as measured by the total number of reversals (Supplementary Fig. Fig. S1).Fig. 2


Abnormal modulation of reward versus punishment learning by a dopamine D2-receptor antagonist in pathological gamblers.

Janssen LK, Sescousse G, Hashemi MM, Timmer MH, ter Huurne NP, Geurts DE, Cools R - Psychopharmacology (Berl.) (2015)

The effect of sulpiride on outcome-specific error rates (i.e., mean error rates on trials following unexpected rewards—mean error rates on trials following unexpected punishment). Sulpiride significantly impairs reward versus punishment learning in controls while not altering the balance between reward and punishment learning in gamblers. Error bars represent 1 SEM; *p < 0.05, ns denotes not significant
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4537492&req=5

Fig2: The effect of sulpiride on outcome-specific error rates (i.e., mean error rates on trials following unexpected rewards—mean error rates on trials following unexpected punishment). Sulpiride significantly impairs reward versus punishment learning in controls while not altering the balance between reward and punishment learning in gamblers. Error bars represent 1 SEM; *p < 0.05, ns denotes not significant
Mentions: Figure 2 shows that sulpiride altered reward versus punishment reversal learning in controls, while not altering reversal learning in gamblers. This observation was substantiated by an ANOVA of the error rates on reversal trials (Table 2), which revealed a significant interaction of group × drug × outcome (F(1,38) = 5.288, p = 0.027). When decomposing the three-way interaction effect into two-way interaction effects for each group, we found that this was driven by a drug × outcome interaction in controls (F(1,21) = 4.768, p = 0.040). By contrast, there was no drug × outcome interaction in gamblers (F(1,17) = 1.183, p = 0.292). The drug × outcome interaction in controls was due to a significant simple main effect of drug on reward learning (F(1,21) = 5.439, p = 0.030), not punishment learning (F(1,21) = 0.523, p = 0.478). Thus, sulpiride induced a shift away from reward learning in controls, while not altering the balance between reward and punishment learning in gamblers. Under placebo there was no group × outcome interaction (F(1,38) = 0.976, p = 0.329). In addition to the outcome-specific effects of sulpiride on reversal learning, there was also an outcome-nonspecific main effect of drug on error rate (F(1,38) = 4.452, p = 0.041). This was due to sulpiride impairing performance across groups and outcomes. This raises the question whether the impairment is specific to reversal trials or extends to non-reversal trials. Supplementary analysis including the within-subjects factor trial type (reversal, non-reversal reward, and non-reversal punishment trials) revealed a significant group × drug × outcome × trial type interaction (F(2,37) = 3.581, p = 0.038). When decomposing this interaction into the simple three-way interaction effect for each trial type, we found that this four-way interaction was driven by a group × drug × outcome interaction for reversal trials only. In line with that, there was no significant effect of group, drug or outcome on performance on non-reversal trials as measured by the total number of reversals (Supplementary Fig. Fig. S1).Fig. 2

Bottom Line: Moreover, pervasive theoretical accounts suggest a key role for dopamine in reversal learning.In line with previous studies, blockade of D2 receptors with sulpiride impaired reward versus punishment reversal learning in controls.By contrast, sulpiride did not have any outcome-specific effects in gamblers.

View Article: PubMed Central - PubMed

Affiliation: Donders Institute for Brain, Cognition and Behavior, Radboud University, PO Box 9101, 6500 HB, Nijmegen, The Netherlands, l.k.janssen@donders.ru.nl.

ABSTRACT

Rationale: Pathological gambling has been associated with dopamine transmission abnormalities, in particular dopamine D2-receptor deficiency, and reversal learning deficits. Moreover, pervasive theoretical accounts suggest a key role for dopamine in reversal learning. However, there is no empirical evidence for a direct link between dopamine, reversal learning and pathological gambling.

Objective: The aim of the present study is to triangulate dopamine, reversal learning, and pathological gambling.

Methods: Here, we assess the hypothesis that pathological gambling is accompanied by dopamine-related problems with learning from reward and punishment by investigating effects of the dopamine D2-receptor antagonist sulpiride (400 mg) on reward- and punishment-based reversal learning in 18 pathological gamblers and 22 healthy controls, using a placebo-controlled, double-blind, counter-balanced design.

Results: In line with previous studies, blockade of D2 receptors with sulpiride impaired reward versus punishment reversal learning in controls. By contrast, sulpiride did not have any outcome-specific effects in gamblers.

Conclusion: These data demonstrate that pathological gambling is associated with a dopamine-related anomaly in reversal learning from reward and punishment.

No MeSH data available.


Related in: MedlinePlus