Lewis and Fischer rats: a comparison of dopamine transporter and receptors levels

Flores, Gonzalo; Wood, Graham K.; Barbeau, David; Quirion, Rémi; Srivastava, Lalit K.

doi:10.1016/s0006-8993(98)01011-7

Cited by 89 publications

(85 citation statements)

References 21 publications

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“…We also observed a similar trend with [ 3 H]WIN 34,428 membrane binding assays: LEW rats had 15-18% fewer maximal DAT binding sites in both dSTR and NAc. Thus, our results support those of Flores et al (1998) and suggest that a strain difference in the number of DATs likely contributes to the difference in basal DAT function in vivo. Recent results in LEW and F344 rats with a cocaine analog also led Haile et al (2005) to speculate that LEW rats might have lower DAT levels.…”

Section: Discussionsupporting

confidence: 87%

“…Thus, one explanation for the reduced DA clearance that we observed in LEW rats is that, relative to F344 rats, LEW rats have fewer functional DATs in dSTR and/or NAc. The literature is equivocal on this issue, however, with one study indicating LEW rats have less DAT binding (Flores et al 1998), but another reporting no strain difference (George et al 1991). Here, using western-blot analysis of DAT immunoreactivity, we found statistically less (∼20%) DAT protein in both dSTR and NAc of LEW, as compared to F344, rats.…”

Section: Discussionmentioning

confidence: 51%

“…Differences in a wide variety of neurochemical systems have been suggested to be important for divergent behaviors in LEW and F344 rats (see Kosten and Ambrosio 2002 for review), but relatively little attention has been given to the role of strain differences in DATs. Indeed, the existing literature is somewhat inconsistent, with one report showing lower DAT binding in dSTR and NAc of LEW rats, compared to F344 rats (Flores et al 1998) and another finding no strain differences (George et al 1991). Recently, however, Haile and colleagues (2005) showed that the selective DAT inhibitor RTI336 alters cocaine-induced behaviors in a strain-dependent manner and suggested that these behavioral effects might reflect differences in NAc DAT levels (Haile et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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Inbred Lewis and Fischer 344 rat strains differ not only in novelty- and amphetamine-induced behaviors, but also in dopamine transporter activity in vivo

2007

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Inbred Lewis (LEW) and Fischer 344 (F344) rats are differentially sensitive to drugs of abuse, making them useful for studying addiction-related neural mechanisms. Here, we investigated whether strain differences in dopamine transporters (DATs) in dorsal striatum (dSTR) and/or nucleus accumbens (NAc) may help to explain their behavioral differences. The behavior of male LEW and F344 rats was assessed in an open-field arena during habituation to novelty and after an i.v. infusion of saline and/or 0.5 mg/kg d-amphetamine (AMPH). In vitro measures of DAT binding, protein and cellsurface expression, as well as in vitro and in vivo measures of function, were used to compare DATs in dSTR and NAc of these two strains. We found that LEW rats exhibited higher novelty-and AMPHinduced locomotion, but F344 rats exhibited greater AMPH-induced rearing and stereotypy. An initial habituation session with i.v. saline minimized the strain differences in AMPH-induced behaviors except that the more frequent AMPH-induced rearing in F344 rats persisted. Strain differences in DAT total protein and basal activity were also observed, with LEW rats having less protein and slower in vivo clearance of locally-applied DA in dSTR and NAc. AMPH inhibited in vivo DA clearance in dSTR and NAc of both strains, but to a greater extent in F344 rats. Taken together, the lower basal DAT function in LEW rats is consistent with their greater novelty-induced locomotor activation, whereas the greater inhibition of DA clearance by AMPH in F344 rats is consistent with their marked AMPH-induced rearing behavior.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 99%

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Inbred Lewis and Fischer 344 rat strains differ not only in novelty- and amphetamine-induced behaviors, but also in dopamine transporter activity in vivo

2007

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“…However, Lindley et al (1999) found no differences in DA in either the core or the shell of the nucleus accumbens. Relative to Fischer 344 rats, Lewis rats have shown lower DA transporter levels in the striatum, nucleus accumbens, and olfactory tubercle (Flores et al, 1998). It remains to be seen, however, whether the extent of any or all of these, or some other difference, may be involved in impulsive choice.…”

Section: Discussionmentioning

confidence: 97%

“…Lewis rats have shown fewer 5-HT 1A binding sites and lower levels of 5-HT in various brain regions (Selim and Bradberry, 1996;Burnet et al, 1996) than Fisher 344 rats. Lewis rats also have shown fewer DA transporters and reduced DA concentrations in specific brain regions (Flores et al, 1998;Lindley et al, 1999). In addition, Lewis rats show greater selfadministration of cocaine, morphine, codeine, and ethanol than Fisher 344 rats (Li and Lumeng, 1984;Kosten et al, 1997;Martin et al, 1999;Suzuki et al, 1988a,b).…”

Section: Introductionmentioning

confidence: 99%

Effects of clomipramine on self-control choice in Lewis and Fischer 344 rats

Anderson

Woolverton

2005

Pharmacology Biochemistry and Behavior

118

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Rates of delay discounting (impulsive choice) have been shown to vary among individuals, particularly people who abuse drugs relative to those who do not, but factors that may contribute to these differences have not been identified. To explore a role for possible genetic and neurochemical determinants, Lewis (n=8) and Fischer 344 (n=8) rats were allowed to choose between one food pellet delivered immediately and three food pellets delivered after increasing delays. The delays to the large reinforcer (0, 10, 20, 40, 60 s) were increased across five blocks of trials in daily experimental sessions. For both groups of rats, choice for the larger reinforcer decreased as the delay to presentation increased. However, the Lewis rats were more likely to choose the smaller, immediate reinforcer earlier in the session, i.e., at shorter large-reinforcer delays, than the Fisher 344 rats. This difference in choice was statistically significant. Repeated administration of 3.0 mg/kg, i.p. clomipramine (mean of last five sessions) did not significantly alter choice, relative to baseline, for either strain. The present findings suggest that differences in delay discounting/impulsive choice may involve genetic, e.g., neurochemical, differences.

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Integrating Behavioral Economics and Behavioral Genetics: Delayed Reward Discounting as an Endophenotype for Addictive Disorders

MacKillop

2012

J Exper Analysis Behavior

109

108

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Delayed reward discounting is a behavioral economic index of impulsivity, referring to how much an individual devalues a reward based on its delay in time. As a behavioral process that varies considerably across individuals, delay discounting has been studied extensively as a model for self-control, both in the general population and in clinical samples. There is growing interest in genetic influences on discounting and, in particular, the prospect of discounting as an endophenotype for addictive disorders (i.e., a heritable mechanism partially responsible for conferring genetic risk). This review assembles and critiques the evidence supporting this hypothesis. Via numerous cross-sectional studies and a small number of longitudinal studies, there is considerable evidence that impulsive discounting is associated with addictive behavior and appears to play an etiological role. Moreover, there is increasing evidence from diverse methodologies that impulsive delay discounting is temporally stable, heritable, and that elevated levels are present in nonaffected family members. These findings suggest that impulsive discounting meets the criteria for being considered an endophenotype. In addition, recent findings suggest that genetic variation related to dopamine neurotransmission is significantly associated with variability in discounting preferences. A significant caveat, however, is that the literature is modest in some domains and, in others, not all the findings have been supportive or consistent. In addition, important methodological considerations are necessary in future studies. Taken together, although not definitive, there is accumulating support for the hypothesis of impulsive discounting as an endophenotype for addictive behavior and a need for further systematic investigation.

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Lewis and Fischer rats: a comparison of dopamine transporter and receptors levels

Cited by 89 publications

References 21 publications

Inbred Lewis and Fischer 344 rat strains differ not only in novelty- and amphetamine-induced behaviors, but also in dopamine transporter activity in vivo

Inbred Lewis and Fischer 344 rat strains differ not only in novelty- and amphetamine-induced behaviors, but also in dopamine transporter activity in vivo

Effects of clomipramine on self-control choice in Lewis and Fischer 344 rats

Integrating Behavioral Economics and Behavioral Genetics: Delayed Reward Discounting as an Endophenotype for Addictive Disorders

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