Limits...
The Impact of Selective Dopamine D2, D3 and D4 Ligands on the Rat Gambling Task.

Di Ciano P, Pushparaj A, Kim A, Hatch J, Masood T, Ramzi A, Khaled MA, Boileau I, Winstanley CA, Le Foll B - PLoS ONE (2015)

Bottom Line: The present study therefore aimed to investigate the effects of selective antagonists and agonists of D2, D3 and D4 receptors in a rodent analogue of the Iowa gambling task used clinically.In this rat gambling task (rGT), animals are trained to associate different response holes with different magnitudes and probabilities of food pellet rewards and punishing time-out periods.Only the D4 drug had modest effects on latency measures suggesting that D4 may contribute in some ways to decision making under this task.

View Article: PubMed Central - PubMed

Affiliation: Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of Toronto, 33 Russell Street, Toronto, Canada M5S 2S1.

ABSTRACT
Gambling is an addictive disorder with serious societal and personal costs. To-date, there are no approved pharmacological treatments for gambling disorder. Evidence suggests a role for dopamine in gambling disorder and thus may provide a therapeutic target. The present study therefore aimed to investigate the effects of selective antagonists and agonists of D2, D3 and D4 receptors in a rodent analogue of the Iowa gambling task used clinically. In this rat gambling task (rGT), animals are trained to associate different response holes with different magnitudes and probabilities of food pellet rewards and punishing time-out periods. As in the Iowa gambling task, the optimal strategy is to avoid the tempting high-risk high-reward options, and instead favor those linked to smaller per-trial rewards but also lower punishments, thereby maximizing the amount of reward earned over time. Administration of those selective ligands did not affect decision making under the rGT. Only the D4 drug had modest effects on latency measures suggesting that D4 may contribute in some ways to decision making under this task.

No MeSH data available.


Related in: MedlinePlus

Effect of administration of a D4 agonist on the rGT.A: Mean ± SEM percent choice on the advantageous choice (dark bars), omissions (grey bars) and premature responses (open bars). Administration of PD168077 produced a dose-dependent decrease in advantageous responses (n = 33; F(4, 128) = 2.992, p = 0.021, one-way ANOVA). B: Mean ± SEM number of trials initiated. No significant effects were found. C: Mean ± SEM latency to make a choice (grey bars) and latency to collect the food pellets (open bars). *Differences were found between the 5mg/kg and 10 mg/kg doses when compared to vehicle (n = 33; p<0.05). D: Ratio ± SEM perseverative responses for punished trials (grey bars) and rewarded trials (open bars). No significant effects were found.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4564230&req=5

pone.0136267.g002: Effect of administration of a D4 agonist on the rGT.A: Mean ± SEM percent choice on the advantageous choice (dark bars), omissions (grey bars) and premature responses (open bars). Administration of PD168077 produced a dose-dependent decrease in advantageous responses (n = 33; F(4, 128) = 2.992, p = 0.021, one-way ANOVA). B: Mean ± SEM number of trials initiated. No significant effects were found. C: Mean ± SEM latency to make a choice (grey bars) and latency to collect the food pellets (open bars). *Differences were found between the 5mg/kg and 10 mg/kg doses when compared to vehicle (n = 33; p<0.05). D: Ratio ± SEM perseverative responses for punished trials (grey bars) and rewarded trials (open bars). No significant effects were found.

Mentions: A two-way Measure (3 levels) X Dose (5 levels) ANOVA revealed an interaction that approached significance when corrected for non-sphericity (Fig 2; F(8, 256) = 2.155, pGG = 0.073; partial eta squared = 0.063). Follow-up analyses revealed that this interaction was due to a significant effect of Dose for the Advantageous choice (F(4, 128) = 2.992, p = 0.021; partial eta squared = 0.086), but not for the other Measures (Fig 2A). t-Tests revealed that Advantageous choices did not differ from vehicle at any dose of PD168077. A one–way ANOVA on the effect of Dose for the number of trials (Fig 2B) revealed no effect, while a two-way Measure (Fig 2D; punishment perseveration, reward perseveration) X Dose ANOVA revealed only an effect of measure (F(1, 32) = 97.532, p<0.001; partial eta squared = .753). An ANOVA on the effect of Measure (collect latency, choice latency) X Dose (5 levels) revealed an interaction (Fig 2C; F(4, 218) = 4.944, p<0.01; partial eta squared = .134), which was due to an effect of Dose on Collect Latency (F(4, 128) = 6.811, p<0.001; partial eta squared = .175) but not Choice Latency. t-Tests comparing vehicle to all doses revealed a difference between vehicle and the 5mg/kg (t(32) = 3.146, p = 0.004) and 10 mg/kg doses (t(32) = 3.621, p = 0.001; Bonferroni corrected p = 0.0125).


The Impact of Selective Dopamine D2, D3 and D4 Ligands on the Rat Gambling Task.

Di Ciano P, Pushparaj A, Kim A, Hatch J, Masood T, Ramzi A, Khaled MA, Boileau I, Winstanley CA, Le Foll B - PLoS ONE (2015)

Effect of administration of a D4 agonist on the rGT.A: Mean ± SEM percent choice on the advantageous choice (dark bars), omissions (grey bars) and premature responses (open bars). Administration of PD168077 produced a dose-dependent decrease in advantageous responses (n = 33; F(4, 128) = 2.992, p = 0.021, one-way ANOVA). B: Mean ± SEM number of trials initiated. No significant effects were found. C: Mean ± SEM latency to make a choice (grey bars) and latency to collect the food pellets (open bars). *Differences were found between the 5mg/kg and 10 mg/kg doses when compared to vehicle (n = 33; p<0.05). D: Ratio ± SEM perseverative responses for punished trials (grey bars) and rewarded trials (open bars). No significant effects were found.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4564230&req=5

pone.0136267.g002: Effect of administration of a D4 agonist on the rGT.A: Mean ± SEM percent choice on the advantageous choice (dark bars), omissions (grey bars) and premature responses (open bars). Administration of PD168077 produced a dose-dependent decrease in advantageous responses (n = 33; F(4, 128) = 2.992, p = 0.021, one-way ANOVA). B: Mean ± SEM number of trials initiated. No significant effects were found. C: Mean ± SEM latency to make a choice (grey bars) and latency to collect the food pellets (open bars). *Differences were found between the 5mg/kg and 10 mg/kg doses when compared to vehicle (n = 33; p<0.05). D: Ratio ± SEM perseverative responses for punished trials (grey bars) and rewarded trials (open bars). No significant effects were found.
Mentions: A two-way Measure (3 levels) X Dose (5 levels) ANOVA revealed an interaction that approached significance when corrected for non-sphericity (Fig 2; F(8, 256) = 2.155, pGG = 0.073; partial eta squared = 0.063). Follow-up analyses revealed that this interaction was due to a significant effect of Dose for the Advantageous choice (F(4, 128) = 2.992, p = 0.021; partial eta squared = 0.086), but not for the other Measures (Fig 2A). t-Tests revealed that Advantageous choices did not differ from vehicle at any dose of PD168077. A one–way ANOVA on the effect of Dose for the number of trials (Fig 2B) revealed no effect, while a two-way Measure (Fig 2D; punishment perseveration, reward perseveration) X Dose ANOVA revealed only an effect of measure (F(1, 32) = 97.532, p<0.001; partial eta squared = .753). An ANOVA on the effect of Measure (collect latency, choice latency) X Dose (5 levels) revealed an interaction (Fig 2C; F(4, 218) = 4.944, p<0.01; partial eta squared = .134), which was due to an effect of Dose on Collect Latency (F(4, 128) = 6.811, p<0.001; partial eta squared = .175) but not Choice Latency. t-Tests comparing vehicle to all doses revealed a difference between vehicle and the 5mg/kg (t(32) = 3.146, p = 0.004) and 10 mg/kg doses (t(32) = 3.621, p = 0.001; Bonferroni corrected p = 0.0125).

Bottom Line: The present study therefore aimed to investigate the effects of selective antagonists and agonists of D2, D3 and D4 receptors in a rodent analogue of the Iowa gambling task used clinically.In this rat gambling task (rGT), animals are trained to associate different response holes with different magnitudes and probabilities of food pellet rewards and punishing time-out periods.Only the D4 drug had modest effects on latency measures suggesting that D4 may contribute in some ways to decision making under this task.

View Article: PubMed Central - PubMed

Affiliation: Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of Toronto, 33 Russell Street, Toronto, Canada M5S 2S1.

ABSTRACT
Gambling is an addictive disorder with serious societal and personal costs. To-date, there are no approved pharmacological treatments for gambling disorder. Evidence suggests a role for dopamine in gambling disorder and thus may provide a therapeutic target. The present study therefore aimed to investigate the effects of selective antagonists and agonists of D2, D3 and D4 receptors in a rodent analogue of the Iowa gambling task used clinically. In this rat gambling task (rGT), animals are trained to associate different response holes with different magnitudes and probabilities of food pellet rewards and punishing time-out periods. As in the Iowa gambling task, the optimal strategy is to avoid the tempting high-risk high-reward options, and instead favor those linked to smaller per-trial rewards but also lower punishments, thereby maximizing the amount of reward earned over time. Administration of those selective ligands did not affect decision making under the rGT. Only the D4 drug had modest effects on latency measures suggesting that D4 may contribute in some ways to decision making under this task.

No MeSH data available.


Related in: MedlinePlus