Cocaine self-administration and locomotor activity are altered in Lewis and F344 inbred rats by RTI 336, a 3-phenyltropane analog that binds to the dopamine transporter
Haile, C. N., Zhang, X. Y., Carroll, F., & Kosten, T. A. (2005). Cocaine self-administration and locomotor activity are altered in Lewis and F344 inbred rats by RTI 336, a 3-phenyltropane analog that binds to the dopamine transporter. Brain Research, 1055(1-2), 186-195.
Lewis and Fischer 344 (F344) rats differ in responses to cocaine and characteristics of the mesolimbic dopamine system. Compared to F344 rats, Lewis rats have lower D-2 receptor and dopamine transporter (DAT) levels in nucleus accumbens (NAc). We showed previously that altering D, and D2 receptor levels pharmacologically had strain-dependent effects on cocaine self-administration. This study tests whether the phenyltropane analog, 3 beta-(4-Chlorophenyl) tropane-2 beta-[3-(4'-methylphenyl) isoxazol-5-yl] Hydrochloride (RTI 336), a potent and selective DAT inhibitor, differentially alters reinforcing, discriminative, and locomotor effects of cocaine in these strains. The effects of RTI 336 pretreatment on cocaine self-administration were assessed under a fixed-ratio (FR) schedule of reinforcement. Its effects on cocaine discrimination were conducted using a two-lever food-reinforced task. Finally, the effects of RTI 336 pretreatment on cocaine-induced locomotor activity were examined. RTI 336 increased cocaine self-administration in F344 rats, while Lewis rats showed reduced intake under the FR schedule. RTI 336 reduced cocaine-induced locomotor activity in Lewis rats but not in F344 rats. RTI 336 did not substitute for or antagonize cocaine's discriminative stimulus effects in either strain. Results show that a DAT inhibitor alters cocaine-induced behaviors in a strain-dependent manner. These effects may relate to inherent differences in NAc DAT levels between Lewis and F344 rats. 0 2005 Elsevier B.V. All rights reserved