Ultraschallvokalisationen im Sign- und Goal-Paradigma und der Einfluss der Cacna1c-Haploinsuffizienz

In this dissertation project, an established rat model for "sign-and goal-tracking" was investigated. In this Pavlovian task, rats show individual differences in sensitivity to the conditional incentive stimulus. So-called sign- and goal-tracker not only respond differently to the presentation of a cue signalling a reward or the reward itself, but also behave differently when expectations are violated during extinction. Classification is based on their approach behavior to either the signal predicting the reward or to the reward itself. Previous studies have shown that the dopaminergic system is involved in the expression of this behavior. In particular, there has been considerable interest in determining the affective state of subjects during task performance. It was investigated whether, what kind and in what frequency ultrasonic vocalizations are emitted during the task and to what extent they were related to sign- and goal-behavior. In addition, we tested if a mutation on the Cacna1c gene, alters behavior in this paradigm. Interactions between genetic and environmental risk factors play an important role in the development of mental disorders. This particular gene, which encodes the α1C-subunit of the L-type voltage-gated calcium channel CaV1.2, is considered to be one of the vulnerability genes for the development of several disorders, among them depressive disorders, autism spectrum disorders, bipolar disorders, and schizophrenia. Previous work suggests that the behavioral changes seen in Cacna1c haploinsufficient rats are at least partly due to changes in the dopaminergic system. We applied this Pavlovian conditioning task in this genetically altered rat model and compared haploinsufficient rats with their wild-type littermates. Subjects emitted appetetive 50-kHz USV during the task. Despite strong interindividual variability in call rate, these were intraindividually stable across paradigms and extinction. Moreover, both the haploinsufficient rats and their littermates showed a clear tendency toward goal-tracking behavior. Individual calling rate was positively associated with sign-tracking and negatively associated with goal-tracking. This suggests an associated personality disposition. There was a genotype difference in call rate. The reduced 50-kHz calls in the Cacna1c haploinsufficient subjects may indicate a reduced affect state due to haploinsufficiency and is consistent with the assumption of altered dopamine signaling in Cacna1c rats. This finding supports the applicability of this model in mental disorders.