title: PRX-00023, a selective serotonin 1A receptor agonist, reduces ultrasonic vocalizations in infant rats bred for high infantile anxiety.
abstract: 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.
authors: Division of Developmental Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA. sab9@columbia.edu
authors: Susan A
authors: SA
authors: Brunelli
authors: Jessica A
authors: JA
authors: Aviles
authors: Kimberly S
authors: KS
authors: Gannon
authors: Aron
authors: A
authors: Branscomb
authors: Sharon
authors: S
authors: Shacham
mesh_terms: D000375:Aging; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000235:genetics; D001008:Anxiety Disorders / Q000188:drug therapy; D001010:Anxiety, Separation / Q000188:drug therapy; D001259:Ataxia / Q000139:chemically induced; D001831:Body Temperature / Q000187:drug effects; D002065:Buspirone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004609:Eliminative Behavior, Animal / Q000187:drug effects; D005260:Female; D006120:Grooming / Q000187:drug effects; D006824:Hybridization, Genetic; D008297:Male; D009068:Movement / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D058825:Serotonin 5-HT1 Receptor Agonists; D012727:Sex Characteristics; D012934:Social Isolation; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D014465:Ultrasonics; D014828:Vocalization, Animal / Q000187:drug effects*
chemical_list: D014151:Anti-Anxiety Agents; D010879:Piperazines; D058825:Serotonin 5-HT1 Receptor Agonists; D013449:Sulfonamides; C511631:naluzotan; D002065:Buspirone