Previous research has shown that Lewis rats make more impulsive choices than Fischer 344 rats. Such strain-related differences in choice are important as they may provide an avenue for exploring genetic and neurochemical contributions to impulsive choice. The present systematic replication was designed to determine if these findings could be reproduced using a procedure less susceptible to within- or between-session carry-over effects that may have affected previous findings. Specifically, delays to the larger-later food reinforcer were manipulated between conditions following steady-state assessments of choice, and the order of delays across conditions was mixed. The results confirmed previous findings that Lewis rats made significantly more impulsive choices than Fischer 344 rats. Fischer 344 rats' preference for the larger-later reinforcer, on the other hand, was less extreme than reported in prior research, which may be due to carry-over effects inherent to the commonly used technique of systematically increasing delays within session. Previously reported across-strain motor differences were reproduced as Lewis rats had shorter latencies than Fischer 344 rats, although these latencies were not correlated with impulsive choice. Parallels between reduced dopamine function in Lewis rats and clinical reports of impulse-control disorders following treatment of Parkinson patients with selective D2/D3 dopamine agonists are discussed.

Oxidative stress can cause methionine oxidation that has been implicated in various proteins malfunctions, if not adequately reduced by the methionine sulfoxide reductase system. Recent evidence has found oxidized methionine residues in neurodegenerative conditions. Previously, we have described elevated levels of brain pathologies and an abnormal walking pattern in the methionine sulfoxide reductase A knockout (MsrA −/− ) mouse. Here we show that MsrA −/− mice have compromised complex task learning capabilities relative to wild-type mice. Likewise, MsrA −/− mice exhibit lower locomotor activity and altered gait that exacerbated with age. Furthermore, MsrA −/− mice were less responsive to amphetamine treatment. Consequently, brain dopamine levels were determined. Surprisingly, relative to wild-type mice, MsrA −/− brains contained significantly higher levels of dopamine up to 12 months of age, while lower level of dopamine was observed at 16 months of age. Moreover, striatal regions of MsrA −/− mice showed an increase of dopamine release parallel to observed dopamine levels. Similarly, the expression pattern of tyrosine hydroxylase activating protein correlated with the age-dependent dopamine levels. Thus, it is suggested that dopamine regulation and signaling pathway are impaired in MsrA −/− mice, which may contribute to their abnormal bio-behavior. These observations may be relevant to age-related neurological diseases associated with oxidative stress.

Rationale 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. Objectives 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, & 0.3 mg/kg) on rat’s choices to earn food reinforcement by completing variable-ratio (i.e., gambling-like) or fixed-ratio response requirements. Results In a condition in which the variable-ratio alternative was rarely selected, all but the lowest dose of pramipexole significantly increased choice of the variable-ratio 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 (variable-ratio: + 0.21 s; fixed-ratio: + 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.

Lewis rats have been shown to make more impulsive choices than Fischer 344 rats in discrete-trial choice procedures that arrange fixed (i.e., nontitrating) reinforcement parameters. However, nontitrating procedures yield only gross estimates of preference, as choice measures in animal subjects are rarely graded at the level of the individual subject. The present study was designed to examine potential strain differences in delay discounting using an adjusting-amount procedure, in which distributed (rather than exclusive) choice is observed due to dynamic titration of reinforcer magnitude across trials. Using a steady-state version of the adjusting-amount procedure in which delay was manipulated between experimental conditions, steeper delay discounting was observed in Lewis rats compared to Fischer 344 rats; further, delay discounting in both strains was well described by the traditional hyperbolic discounting model. However, upon partial completion of the present study, a study published elsewhere (Wilhelm & Mitchell, 2009) demonstrated no difference in delay discounting between these strains with the use of a more rapid version of the adjusting-amount procedure (i.e., in which delay is manipulated daily). Thus, following completion of the steady-state assessment in the present study, all surviving Lewis and Fischer 344 rats completed an approximation of this rapid-determination procedure in which no strain difference in delay discounting was observed.