Serotonin 1B receptor effects on response inhibition are independent of inhibitory learning.

Impulsivity is defined in terms of deficits in instrumental response inhibition, when the inability to withhold an action produces a negative outcome. However, there are many behavioral and cognitive constructs which theoretically could contribute to disordered impulsivity, including Pavlovian responding, which few studies have considered in this context. In the present set of studies, we examine Pavlovian inhibitory learning and excitatory responding in a mouse model for dysregulated impulsivity, specifically, mice lacking the serotonin 1B receptor (5-HTR). Consistent with previous results, we show that these mice display increased impulsivity as measured by premature responding in the operant 5-choice serial reaction time test. In a Pavlovian conditioned inhibition paradigm, they also show a decreased ability to withhold responding, but importantly have an intact ability to learn inhibitory associations. In a Pavlovian appetitive conditioning experiment, 5-HTR knockout mice show normal responding under a positive contingency schedule, however, they display increased responding to cues presented on an independent schedule from reinforcement in a zero contingency schedule. Interestingly this difference does not occur when the cues are explicitly unpaired in a negative contingency schedule, nor during a 25% reinforcement schedule. Overall, while our results show that the deficits in operant response inhibition in mice lacking 5-HTR are likely not due to Pavlovian inhibitory or excitatory learning, it is relevant to consider associative learning in the context of dysregulated impulsive behavior.