naluzotan and Anxiety--Separation

To address the development of early anxiety disorders across the lifespan, the High USV line of rats was bred based on rates of infant ultrasonic vocalization in the 40-50 kHz range of predominant frequencies (USV) to maternal separation at postnatal day (P) 10. In this study, rates of USV in High line infants (pups: Postnatal Day 11+/-1) were compared to those of randomly-bred controls in response to EPIX compound PRX-00023, a unique serotonin (5-HT) agonist, acting exclusively at the 5-HT1A receptor, or buspirone, a nonspecific 5HT1A agonist. After testing, pups were examined for sedation and other drug-related effects. The results indicated that all doses of buspirone reduced USV rates in isolation, consistent with other reports. PRX-00023 significantly reduced USV rates at the lowest doses (0.01-0.05 mg/kg). None of the PRX-00023 doses produced sedation, whereas all but the lowest dose of buspirone (0.1 mg/kg) produced sedation effects. The results suggest that this compound alleviates infantile anxiety-like behavior with great specificity in rats bred for high anxiety/depressive phenotypes by selectively targeting 5-HT1A receptors, possibly by both pre- and post-synaptic mechanisms.

Topics: Aging; Animals; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Anxiety, Separation; Ataxia; Body Temperature; Buspirone; Disease Models, Animal; Dose-Response Relationship, Drug; Eliminative Behavior, Animal; Female; Grooming; Hybridization, Genetic; Male; Movement; Piperazines; Rats; Reaction Time; Serotonin 5-HT1 Receptor Agonists; Sex Characteristics; Social Isolation; Sulfonamides; Ultrasonics; Vocalization, Animal