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Relative to wildtype mice, mice lacking 5-HT1Breceptors (5-HT1BKO) exhibit exaggerated heart rate and body temperature responses to environmental stimuli. In contrast, acoustic startle reactivity is reduced in 5-HT1BKO mice. We combined heart rate and temperature measurement with startle response paradigms in order to elucidate this apparent contradiction. Habituation and footshock-induced sensitization paradigms modulate startle reactivity. Reduced startle reactivity and unaltered habituation in 5-HT1BKO mice were replicated. Heart rate and temperature were unaffected by startle stimuli, but increased markedly in response to transportation and handling procedures. Footshocks caused a mild startle-sensitization and tachycardia in both genotypes. The physiological hyper-reactivity in 5-HT1BKO mice is a subtle phenotypic difference that contrasts with the phenotypic decrease in startle reactivity.

In a previous study it was demonstrated that flesinoxan, a selective serotonin (5-HT)1A receptor agonist, had anxiolytic properties in the fear-potentiated startle paradigm. The present study investigated the putative site of action of flesinoxan in this paradigm. Flesinoxan infused either into the dorsal raphe nucleus or the median raphe nucleus did not affect startle potentiation. Bilateral infusion of flesinoxan into the central nucleus of the amygdala on the other hand, dose-dependently blocked the fear-potentiated startle response. These data indicate that flesinoxan exerts it anxiolytic effects in the fear-potentiated startle paradigm via the central nucleus of the amygdala, whereas the dorsal and median raphe nuclei are not directly involved in this process.