PMID- 27889491 OWN - NLM STAT- MEDLINE DCOM- 20170711 LR - 20181202 IS - 1873-7064 (Electronic) IS - 0028-3908 (Print) IS - 0028-3908 (Linking) VI - 114 DP - 2017 Mar 1 TI - Pramipexole enhances disadvantageous decision-making: Lack of relation to changes in phasic dopamine release. PG - 77-87 LID - S0028-3908(16)30511-1 [pii] LID - 10.1016/j.neuropharm.2016.11.014 [doi] AB - Pramipexole (PPX) is a high-affinity D(2)-like dopamine receptor agonist, used in the treatment of Parkinson's disease (PD) and restless leg syndrome. Recent evidence indicates that PPX increases the risk of problem gambling and impulse-control disorders in vulnerable patients. Although the molecular bases of these complications remain unclear, several authors have theorized that PPX may increase risk propensity by activating presynaptic dopamine receptors in the mesolimbic system, resulting in the reduction of dopamine release in the nucleus accumbens (NAcc). To test this possibility, we subjected rats to a probability-discounting task specifically designed to capture the response to disadvantageous options. PPX enhanced disadvantageous decision-making at a dose (0.3 mg/kg/day, SC) that reduced phasic dopamine release in the NAcc. To test whether these modifications in dopamine efflux were responsible for the observed neuroeconomic deficits, PPX was administered in combination with the monoamine-depleting agent reserpine (RES), at a low dose (1 mg/kg/day, SC) that did not affect baseline locomotor and operant responses. Contrary to our predictions, RES surprisingly exacerbated the effects of PPX on disadvantageous decision-making, even though it failed to augment PPX-induced decreases in phasic dopamine release. These results collectively suggest that PPX impairs the discounting of probabilistic losses and that the enhancement in risk-taking behaviors secondary to this drug may be dissociated from dynamic changes in mesolimbic dopamine release. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Pes, Romina AU - Pes R AD - Dept. of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, United States; Dept. of Biomedical Sciences, Neuroscience Division, University of Cagliari, Italy. FAU - Godar, Sean C AU - Godar SC AD - Dept. of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, United States; Dept. of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, United States. FAU - Fox, Andrew T AU - Fox AT AD - Dept. of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, United States. FAU - Burgeno, Lauren M AU - Burgeno LM AD - Dept. of Pharmacology, University of Washington, Seattle, WA, United States. FAU - Strathman, Hunter J AU - Strathman HJ AD - Dept. of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, United States. FAU - Jarmolowicz, David P AU - Jarmolowicz DP AD - Problem Gambling Research Studies (ProGResS) Network, University of Kansas, Lawrence, KS, United States; Dept. of Applied Behavioral Science, University of Kansas, Lawrence, KS, United States. FAU - Devoto, Paola AU - Devoto P AD - Dept. of Biomedical Sciences, Neuroscience Division, University of Cagliari, Italy. FAU - Levant, Beth AU - Levant B AD - Dept. of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States. FAU - Phillips, Paul E AU - Phillips PE AD - Dept. of Pharmacology, University of Washington, Seattle, WA, United States; Dept. of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States. FAU - Fowler, Stephen C AU - Fowler SC AD - Dept. of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, United States. FAU - Bortolato, Marco AU - Bortolato M AD - Dept. of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, United States; Problem Gambling Research Studies (ProGResS) Network, University of Kansas, Lawrence, KS, United States; Dept. of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, United States. Electronic address: marco.bortolato@utah.edu. LA - eng GR - R01 DA039687/DA/NIDA NIH HHS/United States GR - UL1 RR033179/RR/NCRR NIH HHS/United States GR - UL1 TR000001/TR/NCATS NIH HHS/United States GR - P20 GM103638/GM/NIGMS NIH HHS/United States GR - R01 MH104603/MH/NIMH NIH HHS/United States GR - P30 HD002528/HD/NICHD NIH HHS/United States PT - Journal Article DEP - 20161123 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Benzothiazoles) RN - 0 (Receptors, Dopamine D2) RN - 333DO1RDJY (Serotonin) RN - 83619PEU5T (Pramipexole) RN - VTD58H1Z2X (Dopamine) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Animals MH - Benzothiazoles/*administration & dosage MH - Caudate Nucleus/metabolism MH - Decision Making/*drug effects/*physiology MH - Dopamine/metabolism/*physiology MH - Male MH - Norepinephrine/metabolism MH - Nucleus Accumbens/drug effects/metabolism/*physiology MH - Parkinson Disease/complications MH - Pramipexole MH - Prefrontal Cortex/metabolism MH - Probability MH - Putamen/metabolism MH - Rats MH - Rats, Long-Evans MH - Receptors, Dopamine D2/*agonists MH - *Risk-Taking MH - Serotonin/metabolism PMC - PMC5241163 MID - NIHMS834086 OTO - NOTNLM OT - Dopamine OT - Nucleus accumbens OT - Pramipexole OT - Probability discounting OT - Risk taking EDAT- 2016/11/28 06:00 MHDA- 2017/07/14 06:00 PMCR- 2018/03/01 CRDT- 2016/11/28 06:00 PHST- 2016/08/02 00:00 [received] PHST- 2016/11/15 00:00 [revised] PHST- 2016/11/21 00:00 [accepted] PHST- 2016/11/28 06:00 [pubmed] PHST- 2017/07/14 06:00 [medline] PHST- 2016/11/28 06:00 [entrez] PHST- 2018/03/01 00:00 [pmc-release] AID - S0028-3908(16)30511-1 [pii] AID - 10.1016/j.neuropharm.2016.11.014 [doi] PST - ppublish SO - Neuropharmacology. 2017 Mar 1;114:77-87. doi: 10.1016/j.neuropharm.2016.11.014. Epub 2016 Nov 23.