Melanie Tremblay1,2, Michael M Barrus3, Paul J Cocker3,4, Christelle Baunez5, Catharine A Winstanley6. 1. Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Westbrook Mall, Vancouver, BC, V6T 1Z3, Canada. mel.tremblay@utoronto.ca. 2. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. mel.tremblay@utoronto.ca. 3. Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Westbrook Mall, Vancouver, BC, V6T 1Z3, Canada. 4. Department of Experimental Psychology, University of Cambridge, Cambridge, UK. 5. Institut de Neurosciences de la Timone (INT), UMR7289, Centre National de la Recherche Scientifique (CNRS) ∓ Aix-Marseille Université (AMU), Marseille, France. 6. Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Westbrook Mall, Vancouver, BC, V6T 1Z3, Canada. cwinstanley@psych.ubc.ca.
Abstract
RATIONALE: Chronic administration of D2/3 receptor agonists ropinirole or pramipexole can increase the choice of uncertain rewards in rats, theoretically approximating iatrogenic gambling disorder (iGD). OBJECTIVES: We aimed to assess the effect of chronic ropinirole in animal models that attempt to capture critical aspects of commercial gambling, including the risk of losing rather than failing to gain, and the use of win-paired sensory stimuli heavily featured in electronic gambling machines (EGMs). METHODS: Male Long-Evans rats learned the rat gambling task (rGT; n = 24), in which animals sample between four options that differ in the magnitude and probability of rewards and time-out punishments. In the cued rGT (n = 40), reward-concurrent audiovisual cues were added that scaled in complexity with win size. Rats were then implanted with an osmotic pump delivering ropinirole (5 mg/kg/day) or saline for 28 days. RESULTS: Chronic ropinirole did not unequivocally increase preference for more uncertain outcomes in either the cued or uncued rGT. Ropinirole transiently increased premature responses, a measure of motor impulsivity, and this change was larger and more long-lasting in the cued task. CONCLUSIONS: These data suggest that explicitly signaling loss prevents the increase in preference for uncertain rewards caused by D2/3 receptor agonists observed previously. The ability of win-paired cues to amplify ropinirole-induced increases in motor impulsivity may explain why compulsive use of EGMs is particularly common in iGD. These data offer valuable insight into the cognitive-behavioral mechanisms through which chronic dopamine agonist treatments may induce iGD and related impulse control disorders.
RATIONALE: Chronic administration of D2/3 receptor agonists ropinirole or pramipexole can increase the choice of uncertain rewards in rats, theoretically approximating iatrogenic gambling disorder (iGD). OBJECTIVES: We aimed to assess the effect of chronic ropinirole in animal models that attempt to capture critical aspects of commercial gambling, including the risk of losing rather than failing to gain, and the use of win-paired sensory stimuli heavily featured in electronic gambling machines (EGMs). METHODS: Male Long-Evans rats learned the rat gambling task (rGT; n = 24), in which animals sample between four options that differ in the magnitude and probability of rewards and time-out punishments. In the cued rGT (n = 40), reward-concurrent audiovisual cues were added that scaled in complexity with win size. Rats were then implanted with an osmotic pump delivering ropinirole (5 mg/kg/day) or saline for 28 days. RESULTS: Chronic ropinirole did not unequivocally increase preference for more uncertain outcomes in either the cued or uncued rGT. Ropinirole transiently increased premature responses, a measure of motor impulsivity, and this change was larger and more long-lasting in the cued task. CONCLUSIONS: These data suggest that explicitly signaling loss prevents the increase in preference for uncertain rewards caused by D2/3 receptor agonists observed previously. The ability of win-paired cues to amplify ropinirole-induced increases in motor impulsivity may explain why compulsive use of EGMs is particularly common in iGD. These data offer valuable insight into the cognitive-behavioral mechanisms through which chronic dopamine agonist treatments may induce iGD and related impulse control disorders.
Authors: J V Ramji; J P Keogh; T J Blake; C Broom; R J Chenery; D R Citerone; V A Lewis; A C Taylor; S E Yeulet Journal: Xenobiotica Date: 1999-03 Impact factor: 1.908
Authors: M Scarselli; F Novi; E Schallmach; R Lin; A Baragli; A Colzi; N Griffon; G U Corsini; P Sokoloff; R Levenson; Z Vogel; R Maggio Journal: J Biol Chem Date: 2001-05-23 Impact factor: 5.157