title: Acute, but not repeated, administration of the neurotensin NTS1 receptor agonist PD149163 decreases conditioned footshock-induced ultrasonic vocalizations in rats.
abstract: Neurotensin is an endogenous neuropeptide that has significant interactions with monoamine neurotransmitter systems. To date, neurotensin NTS1 receptor agonists, such as PD149163, have been primarily evaluated for the treatment for schizophrenia, drug addiction, and pain. Recently, PD149163 was found to attenuate fear-potentiated startle in rats, an experimental procedure used for screening anxiolytic drugs. The present study sought to assess these findings through testing PD149163 in a conditioned footshock-induced ultrasonic vocalization (USV) model. Conditioning was conducted in male Wistar rats using chambers equipped with shock grid floors and an ultrasonic vocalization detector. PD149163 and the 5-HT1A receptor partial agonist buspirone produced a statistically significant reduction of 22kHz USV counts. The typical antipsychotic haloperidol also reduced 22kHz USV counts, but did so at cataleptic doses. Ten days of repeated administration of PD149163 abolished the inhibitory effects of PD149163 on 22kHz USVs. These findings further support an anxiolytic profile for PD149163. However, tolerance to these effects may limit the utility of these drugs for the treatment of anxiety.
authors.affiliation: Psychology Department, Northern Michigan University, Marquette, MI, USA. Electronic address: aprus@nmu.edu.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Prus
authors.affiliation: Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Hillhouse
authors.affiliation: School of Psychology, Arizona State University, Phoenix, AZ, USA.
authors.forename: Amber L
authors.initials: AL
authors.lastname: LaCrosse
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology; D002065:Buspirone / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced; D003213:Conditioning, Psychological / Q000187:drug effects*; D004361:Drug Tolerance; D004597:Electroshock; D005239:Fear; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009496:Neurotensin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018028:Receptors, Neurotensin / Q000819:agonists*; D014828:Vocalization, Animal / Q000187:drug effects*
chemical_list: D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; C117269:PD 149163; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin; D006220:Haloperidol; D002065:Buspirone
keywords: Anxiety; Buspirone; Neurotensin; PD149163; USV; Ultrasonic vocalization; VEH; Vehicle