title: Neurotensin NTS1and NTS2receptor agonists produce anxiolytic-like effects in the 22-kHz ultrasonic vocalization model in rats.
abstract: Neurotensin is a neuropeptide neurotransmitter that interacts with multiple neurotransmitter systems, including those regulating amygdalar function, via NTS1and NTS2receptors. Both receptors are expressed in the amygdala and agonists for NTS1or NTS2receptors have exhibited anxiolytic effects in animal models. Systemic adminstration of NTS1receptor agonist PD149163 was recently shown to reduce footshock conditioned 22-kHz ultrasonic vocalizations in rats, suggesting that PD149163 produced an anxiolytic effect. The effects that neurotensin may have or a selective NTS2receptor agonist may have on 22-kHz vocalizations has yet to be examined. The current study evaluated the effects of intracerebroventricularly administered neurotensin (0.1-10.0μg), PD149163 (0.1-10.0ng), or the NTS2receptor agonist JMV-431 (0.1-1.0μg) on footshock conditioned 22-kHz vocalizations in male Wistar rats. Neurotensin, PD149163, and JMV-431 all significantly reduced the number 22-kHz calls. No changes in call duration were found, suggesting that non-specific drug effects do not account for the reductions in 22-kHz calls. These data support anxiolytic effects produced by activation of NTS1or NTS2receptors, and suggest that neurotensin plays a natural role in the expression of conditioned USVs. These data suggest that both receptor subtypes are putative pharmacologic targets.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, United States.
authors.forename: Floyd F
authors.initials: FF
authors.lastname: Steele
authors.affiliation: Psychology Department, Northern Michigan University, Marquette, MI, United States.
authors.forename: Shannon C
authors.initials: SC
authors.lastname: Whitehouse
authors.affiliation: Psychology Department, Northern Michigan University, Marquette, MI, United States.
authors.forename: Jacob S
authors.initials: JS
authors.lastname: Aday
authors.affiliation: Psychology Department, Northern Michigan University, Marquette, MI, United States. Electronic address: aprus@nmu.edu.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Prus
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002408:Catheters, Indwelling; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D005239:Fear / Q000187:drug effects / Q000502:physiology; D005528:Foot; D057967:Infusions, Intraventricular; D008297:Male; D009496:Neurotensin / Q000031:analogs & derivatives / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D017208:Rats, Wistar; D018028:Receptors, Neurotensin / Q000819:agonists* / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism; D014465:Ultrasonics; D014828:Vocalization, Animal / Q000187:drug effects* / Q000502:physiology
chemical_list: D014151:Anti-Anxiety Agents; C000621669:Boc-Arg-Arg-Pro-Tyr-psi(CH2NH)-Ile-Leu; D018377:Neurotransmitter Agents; C099727:Ntsr2 protein, rat; C117269:PD 149163; D010446:Peptide Fragments; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin
keywords: Anxiety; NTS(1) receptor; NTS(2) receptor; Neurotensin; Ultrasonic vocalization