This proposal describes research designed to determine whether the previously observed large and stable inter-individual differences in basal and cocaine-stimulated extracellular dopamine (DA) levels in rat nucleus accumbens (NAC) and frontal cortex (FCTX) are related to the previously described large and stable inter-individual differences observed in rat cocaine consumption during two-bottle choice experiments. A considerable body of evidence suggests that the behavioral effects of cocaine are mediated by increased dopaminergic transmission in NAC and FCTX; however, direct evidence that mesocorticolimbic dopaminergic transmission correlates with voluntary cocaine consumption is lacking. This proposal describes experiments in which rats are characterized by basal extracellular NAC and FCTX (microdialyzate) DA levels and studied with respect to the response of these levels to an acute injection of cocaine. Subsequently, these same rats will be subjected to a two-bottle choice paradigm in order to determine voluntary cocaine intake. It is hypothesized that rats with lowest baseline levels of extracellular DA in NAC and FCTX will exhibit greatest percentage increases in levels of extracellular DA in response to an acute intraperitoneal cocaine injection and will voluntarily consume relatively large amounts of cocaine in the two-bottle choice experiments. Conversely, rats with highest basal extracellular DA levels in NAC and FCTX are predicted to exhibit smallest percentage increases in cocaine-stimulated extracellular DA levels and consume relatively small amounts of cocaine in the two-bottle choice experiments. If these experiments confirm the hypotheses presented, then a direct link will be established between cocaine preference and dopaminergic transmission in the mesocorticolimbic system. Furthermore, experimental support for these hypotheses will provide the impetus and rationale for additional studies to investigate mechanistic aspects of this relationship.
| Ferraro, T N; Golden, G T; Berrettini, W H et al. (2000) Cocaine intake by rats correlates with cocaine-induced dopamine changes in the nucleus accumbens shell. Pharmacol Biochem Behav 66:397-401 |
