Effects of acute pramipexole on preference for gambling-like schedules of reinforcement in rats.
BACKGROUND
Pramipexole and other direct dopamine agonist medications have been implicated in the development of impulsive behavior such as pathological gambling among those taking the drug to control symptoms of Parkinson's disease or restless leg syndrome. Few laboratory studies examining pramipexole's effects on gambling-like behavior have been conducted.


OBJECTIVE
The present study used a rodent model approximating some aspects of human gambling to examine within-subject effects of acute pramipexole (0.03, 0.1, 0.18, and 0.3 mg/kg) on rat's choices to earn food reinforcement by completing variable-ratio (VR; i.e., gambling-like) or fixed-ratio (FR) response requirements.


RESULTS
In a condition in which the VR alternative was rarely selected, all but the lowest dose of pramipexole significantly increased choice of the VR alternative (an average of 15% above saline). The same doses did not affect choice significantly in a control condition designed to evaluate the involvement of nonspecific drug effects. Pramipexole increased latencies to initiate trials (+9.12 s) and to begin response runs on forced-choice trials (VR = +0.21 s; FR = +0.88 s), but did not affect measures of response perseveration (conditional probabilities of "staying").


CONCLUSIONS
The findings are consistent with clinical reports linking pramipexole to the expression of increased gambling in humans. Results are discussed in the context of neurobehavioral evidence suggesting that dopamine agonists increase sensitivity to reward delay and disrupt appropriate feedback from negative outcomes.
Johnson
Patrick S
PS
Department of Applied Behavioral Science, University of Kansas, 1000 Sunnyside Avenue, Lawrence, KS 66045, USA. pastejohn@ku.edu
Madden
Gregory J
GJ
Brewer
Adam T
AT
Pinkston
Jonathan W
JW
Fowler
Stephen C
SC
D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005715:Gambling / Q000188:drug therapy*; D008297:Male; D000077487:Pramipexole; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule
D052160:Benzothiazoles; D018491:Dopamine Agonists; D000077487:Pramipexole
Eur J Pharmacol. 2009 Aug 15;616(1-3):134-40
19549514
Science. 2007 Nov 23;318(5854):1309-12
17962524
J Exp Anal Behav. 1996 Nov;66(3):283-95
8921612
Sleep. 2010 Jan;33(1):81-7
20120624
J Psychopharmacol. 2007 Jul;21(5):501-6
17446202
J Pharmacol Exp Ther. 2009 Apr;329(1):210-7
19136638
Parkinsonism Relat Disord. 2005 Sep;11(6):381-6
16109498
Clin Neuropharmacol. 2007 Sep-Oct;30(5):249-55
17909302
Parkinsonism Relat Disord. 2007 Dec;13(8):516-9
17544807
Mov Disord. 2006 Dec;21(12):2206-8
17013907
Depress Anxiety. 2000;11(2):58-65
10812530
Mov Disord. 2006 Apr;21(4):524-9
16261618
J Sex Med. 2009 Apr;6(4):1177-1180
18466265
Psychopharmacology (Berl). 2009 Mar;202(4):611-20
18836703
Psychopharmacology (Berl). 2007 Aug;193(2):159-70
17393143
Nature. 1990 Sep 13;347(6289):146-51
1975644
J Gambl Stud. 2008 Dec;24(4):411-22
18561000
Mov Disord. 2000 Sep;15(5):869-72
11009192
Exp Clin Psychopharmacol. 2010 Jun;18(3):267-76
20545391
Neuropsychologia. 2006;44(10):1663-73
16730032
Pharmacol Biochem Behav. 2000 Nov;67(3):637-45
11164096
Neuropsychopharmacology. 2009 Jul;34(8):2041-52
19262467
PLoS One. 2008 Jun 25;3(6):e2479
18575579
J Neurol Neurosurg Psychiatry. 2000 Apr;68(4):423-8
10727476
J Exp Anal Behav. 1968 Jan;11(1):1-8
5636851
Arch Neurol. 2005 Sep;62(9):1377-81
16009751
Psychopharmacology (Berl). 2004 Jul;174(3):341-57
14985929
Neurology. 2003 Aug 12;61(3):422-3
12913220
Behav Res Methods. 2005 Aug;37(3):379-84
16405133
J Gambl Stud. 2009 Sep;25(3):425-31
19241148
Eur Neuropsychopharmacol. 1998 May;8(2):113-20
9619689
J Clin Psychopharmacol. 2008 Feb;28(1):45-51
18204340
Biol Psychiatry. 2004 Jul 1;56(1):54-60
15219473
Psychopharmacology (Berl). 2010 Jan;207(4):645-59
19838863
J Exp Anal Behav. 1984 Nov;42(3):435-52
16812401
CNS Drugs. 2008;22(5):407-16
18399709
Compr Psychiatry. 2010 Mar-Apr;51(2):115-20
20152290
Psychopharmacology (Berl). 2008 Feb;196(2):221-32
17909750
Clin Ther. 2006 Aug;28(8):1065-1078
16982285
Neuropsychopharmacology. 2010 Feb;35(3):591-604
19940844