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

Abstract

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.

Strain differences in delay discounting between Lewis and Fischer 344 rats at baseline and following acute and chronic administration of d-amphetamine

“…Cocaine and amphetamine administration also increased basal levels of DA in the nucleus accumbens shell and core to a greater extent in LEW compared to F344 rats (Cadoni and Di Chiara, 2007). In vivo examination of DA transporters in the dorsal striatum and nucleus accumbens revealed that LEW cleared locally applied DA at a slower rate than F344 rats; however, DA clearance following amphetamine administration was inhibited more in F344 compared to LEW rats (Gulley et al, 2007). …”

Changes in hyporesponsiveness to acute amphetamine and age differences in tyrosine hydroxylase immunoreactivity in the brain over adolescence in male and female rats

“…Different levels of tyrosine hydroxylase in the nucleus accumbens have been reported for different strains of rats (Beitner-Johnson, Guitart, & Nestler, 1991;Gulley, Everett, & Zahniser, 2007) and for rats that differ in activity in a novel environment and after amphetamine treatment (apomorphine susceptible/unsusceptible rats: van der Elst, Roubos, Ellenbroek, Veening, & Cools, 2005; high/low responders: , indicating that this enzyme may also be a good marker for age differences in amphetamine sensitivity. Thus, in experiment 3, we measured tyrosine hydroxylase immunoreactivity in brain regions associated with the increase in locomotor activity after amphetamine, including the core of the nucleus accumbens (Sellings & Clarke, 2003) and the striatum (Rebec, White, & Puotz, 1997), as well as the medial prefrontal cortex, which has been implicated in regulation of activity in these brain regions (Pierce & Kalivas, 1997).…”

Amphetamine and Methamphetamine Differentially Affect Dopamine Transporters in Vitro and in Vivo

“…In vivo clearance of locally applied DA was measured in outbred male Sprague-Dawley rats (n ϭ 52, mean weight ϭ 262 Ϯ 10 g; Charles River Laboratories, Wilmington, MA) using electrochemical methods described in detail elsewhere (34,35). Animals were housed on a 12-h light/dark cycle (lights on at 0600 h) with ad libitum food and water.…”