Increased tyrosine hydroxylase abundance in the ventral tegmental area after taste-immune associative learning with saccharin or sucrose in rats

Abstract

Several animal studies have already demonstrated classical conditioning of immune responses, when a novel sweet solution was paired with the administration of an immunosuppressive drug. However, since sweet solutions are known to have an impact on central dopamine synthesis, their “neutrality” as conditioned stimuli has been questioned. In particular, it is not clear whether even re-exposure to water is sufficient to influence central dopamine synthesis when animals are on a specific fluid-restricted conditioning schedule and whether re-exposure to saccharin or sucrose has similar or different effects. To address this, we conducted a taste-immune associative learning study in rats, using saccharin or sucrose and the immunosuppressive drug fingolimod. Subsequently, we analyzed central tyrosine hydroxylase (TH) abundance and phosphorylation (pTH) to indirectly assess dopamine production. Moreover, we measured central monoamine oxidase A (MAO-A) abundance, thereby gaining information of possible immediate conversion of synthesized dopamine. Western blot analyses of the ventral tegmental area revealed no differences in pTH abundance among fluid-restricted rats that received either water, sucrose, saccharin or fingolimod. However, TH abundance was significantly increased in animals re-exposed to sucrose and saccharin compared to those given water. MAO-A abundance did not differ between groups. Analyses of the abundance and phosphorylation of dopamine-associated enzymes in the ventral and dorsal striatum, showed no differences between groups. These exploratory findings suggest that the consumption of sucrose and saccharin may be more rewarding than water consumption, when rats are maintained on a specific fluid-restricted conditioning schedule. However, further research is necessary to draw precise conclusions.