Operant learning and differential-reinforcement-of-low-rate 36-s responding in 5-HT1A and 5-HT1B receptor knockout mice.

Previous studies with mice lacking 5-HT(1A) (1AKO) and 5-HT(1B) (1BKO) receptors in hippocampus-dependent learning and memory paradigms, suggest that these receptors play an important role in learning and memory, although their precise role is unclear. In the present study, 1AKO and 1BKO mice were studied in operant behavioural paradigms of decision making and response inhibition, to further study the putative involvement of these receptors in prefrontal cortex-dependent learning and memory. Moreover, because 1AKO mice have been shown to exhibit an antidepressant-like phenotype and 1BKO mice to be more impulsive in ethological studies, mice were trained in a differential-reinforcement-of-low-rates (DRL) procedure. Overall, results indicate that 1AKO and 1BKO mice display subtle differences in operant paradigms of decision making and response inhibition compared to wild type (WT) mice. In addition, when responding under a DRL 36-s schedule had stabilised, 1BKO mice showed a phenotype indicative of increased impulsivity, whereas 1AKO mice did not differ from WT mice. In conclusion, 5-HT(1B) receptors appear to play an important role in impulsivity and a minor role in prefrontal cortex-dependent learning and memory as shown by the results obtained in serial reversal learning and extinction. In contrast, 5-HT(1A) receptors appear to be involved in facilitation of autoshaping, but their role in impulsivity and prefrontal cortex-dependent learning and memory appears to be limited.