Strain differences in mesotelencephalic dopaminergic neuronal regulation between Fischer 344 and Lewis rats

Differences in the behavioral responses of Lewis and Fischer (F334) inbred rat strains to stress and psychoactive drugs have been related to differenc es in the expression of various regulatory proteins in regions containing m esolimbic dopamine (DA) neurons. The present study compared basal and stimu lated neurochemical estimates of DA utilization and synthesis in mesocortic al, mesolimbic and nigrostriatal DA terminal regions of these two strains. In unstressed control animals, the Lewis strain had lower DA concentrations in the dorsal striatum (ST; 80.3% of F344) and lower basal dihydroxyphenyl alanine (DOPA) accumulation after m-hydroxybenzylhydrazine (NSD 1015) treat ment in the medial prefrontal cortex (mPfx; 75.3% of F344). Similar differe nces were observed in vehicle-injected animals. No strain differences in ba sal neurochemistry were apparent in the nucleus accumbens shell (NAs) or co re (NAc). In response to restraint stress, dihydroxyphenylacetic acid (DOPA C) to DA ratios in the mPfx, NAs and ST increased in the F344 but not the L ewis strain. However, restraint stress did not significantly increase DOPA accumulation in the F344 strain. This latter finding was not due to a defic it in synthesis capacity, as gamma-hydroxybutyric acid lactone (GBL) increa sed DOPA accumulation significantly more in F344 than Lewis animals. Finall y, haloperidol increased DA utilization similarly in the two strains. Toget her these findings suggest that the inbred, behaviorally divergent F344 and Lewis rats have selective differences in mesocortical, nigrostriatal and m esolimbic DA neuronal regulation. (C) 1999 Published by Elsevier Science B. V. All rights reserved.