Perseverative instrumental and Pavlovian responding to conditioned stimuli in serotonin transporter knockout rats

Environmental stimuli can influence behavior via the process of Pavlovian conditioning. Recent genetic research suggests that some individuals are more sensitive to environmental stimuli for behavioral guidance than others. One important mediator of this effect is serotonin transporter (5-HTT) genetic variance, which increases sensitivity to Pavlovian conditioned stimuli through changes in the build-up of corticolimbic circuits. As these stimuli can have reinforcing effects on instrumental responding, we here investigated their effects on instrumental behavior in 5-HTT knockout rats and their wild-type counterparts by means of the signal attenuation paradigm. In this paradigm animals acquired a Pavlovian association between a stimulus and food reward, and subsequently they had to lever press in order to gain access to this food reward-associated stimulus. Thereafter, half of the animals underwent extinction training during which extinction of the primary Pavlovian association was induced via non-reinforced stimulus presentations, whereas the other half did not receive this training. During a final test session all animals were tested for instrumental responding for the non-reinforced Pavlovian conditioned stimulus, as well as instrumental and Pavlovian responding to the stimulus after an initial lever-press. No genotype differences were observed during the training and extinction sessions. However, during the test session 5-HTT knockout rats that had not received prior extinction training displayed excessive instrumental responding. This was specifically observed during presentation of the stimulus (induced by the first lever press) and was accompanied by an increased number of feeder visits after termination of the stimulus presentation. An additionally performed c-Fos immunohistochemistry study revealed that the behaviors in these animals were associated with abnormal c-Fos immunoreactivity in the orbitofrontal cortex and basolateral amygdala, regions important for the acquisition and maintenance of Pavlovian conditioned stimuli. These findings complement earlier findings showing that 5-HTT knockout animals' behavior is heavily influenced by environmental stimuli and indicate that this extends to the instrumental domain.