Fischer and Lewis rat strains differ in basal levels of neurofilament proteins and their regulation by chronic morphine in the mesolimbic dopamine system

Abstract

We studied levels of neurofilament (NF) proteins in the ventral tegmental area (VTA), and other regions of the central nervous system, of two genetically inbred rat strains, Lewis (LEW) and Fischer (F344) rats. These strains represent genetically divergent populations of rats that have been used to study possible genetic factors involved in a variety of biological processes, including drug addiction: compared to F344 rats, LEW rats show a much higher preference for several classes of drugs of abuse. We found 30-50% lower levels of three NF proteins, NF-200 (NF-H), NF-160 (NF-M), and NF-68 (NF-L), in the VTA of LEW compared to F344 rats by use of immunolabeling and Coomassie blue staining. These strain differences were highly specific to this brain region, with no differences observed elsewhere in brain or spinal cord. Interestingly, chronic treatment of F344 rats with morphine decreased levels of these three NF proteins in the VTA, as found previously in outbred Sprague-Dawley rats (Beitner-Johnson, D., Guitart, X., and Nestler, E.J.:J. Neurosci., 12:2165-2176, 1992), whereas morphine had no effect on NF levels in the VTA of LEW rats. A similar strain difference was observed in chronic morphine regulation of tyrosine hydroxylase, with morphine increasing enzyme immunoreactivity in the VTA of F344 rats (as has been observed previously in Sprague-Dawley rats [Beitner-Johnson, D., and Nestler, E.J.:J. Neurochem., 57:344-347, 1991]), but not in LEW rats. In view of the observations that LEW and F344 rats show different levels of preference for several types of drugs of abuse, and of the evidence supporting a central role of the mesolimbic dopamine system in drug reward mechanisms, the results of the current study suggest the possibility that levels of NFs and tyrosine hydroxylase may mediate some aspects of drug reinforcement and contribute to individual genetic differences in vulnerability to drug addiction.

Effects of cocaine place conditioning, chronic escalating-dose “binge” pattern cocaine administration and acute withdrawal on orexin/hypocretin and preprodynorphin gene expressions in lateral hypothalamus of Fischer and Sprague–Dawley rats

“…The SD rat chosen was also based on our pilot study, in which SD rats showed significant CPP for cocaine at 10 mg/kg, whereas Fischer 344 (F344) rats did not. This is consistent with previous reports by others (Guitart et al, 1992;Kosten et al, 1994;Harris et al, 2005).…”

Molecular Neurobiology of Drug Addiction

“…11, NO.2 The importance of genetic factors in establishing individual responsiveness to drugs of abuse is indicated by differences in drug-related behaviors among differ· ent inbred animal strains (e.g., Lewis and Fischer rat s). The Lewis rat self-administers opiates, cocaine, and al cohol to a greater extent than the Fischer rat (George and Goldberg 1989), and develops a greater degree of conditioned place preference to cocaine and morphine (Guitart et al 1992;Kosten et al 1994). The Lewis rat also exhibits a greater facilitation in brain self-stimu· lation thresholds in response to cannabinoids than the Fischer rat (Gardner and Lowinson 1991).…”

“…Genetic and environmental factors cannot be viewed as separate, independent variables; rather, it is the in teraction between the two that determines an individ ual's predilection for drug addiction. An illustration of such interactions are the fmdings that chronic exposure to drugs of abuse or to glucocorticoids produces diff er ent behavioral effects, and different biochemical adap tations in the mesolimbic dopamine system, in Lewis and Fischer rats (Guitart et al 1992(Guitart et al , 1993Ortiz and Nes tler 1993). In this way, Lewis and Fischer rats provide a novel experimental system to investigate the specifIc genetic and environmental factors that combine to de termine the biochemical phenotype in the mesolimbic dopamine system and the various drug-related be haviors regulated via this neural pathway.…”

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

“…For example, compared to LEW rats, F344 rats are reported to have greater AMPH-induced locomotion at doses between 1 and 2 mg/kg (George et al, 1991;Miserendino et al, 2003; but see Camp et al, 1994, for methamphetamine). LEW rats, in contrast, tend to exhibit greater behavioral sensitization after repeated cocaine or methamphetamine treatment (Camp et al 1994;Kosten et al 1994;Haile et al 2001) and enhanced conditioned place preference for cocaine, nicotine and morphine (Guitart et al 1992;Kosten et al 1994;Horan et al 1997). Furthermore, LEW rats acquire intravenous (i.v.)…”