title: Endogenous neurotensin is involved in estrous cycle related alterations in prepulse inhibition of the acoustic startle reflex in female rats.
abstract: Ovarian hormones regulate prepulse inhibition (PPI) of the acoustic startle reflex. Results from studies in intact female rodents investigating sex, estrous cycle and ovarian hormone regulation of PPI are inconsistent. In experiment #1, we investigated whether PPI in female rats is influenced by the time of day of testing and the estrous cycle stage of the rat. PPI was examined across the day of proestrus (P) and diestrus 1 (D1) in female rats and compared to males. PPI in males and P females was significantly higher than in D1 females. PPI in males and D1 females was significantly affected by the time of day of testing with PPI being reduced in the afternoon and evening compared to morning. PPI in P females was not significantly affected by the time of day of testing. Previous studies have demonstrated estrous cycle regulation of central nervous system neurotensin (NT) neurons and peripherally administered NT receptor agonists regulate PPI in a manner similar to antipsychotic drugs. Experiment #2 of this study was designed to examine whether endogenous NT is involved in estrous cycle regulation of PPI. The NT receptor antagonist SR 142948A reduced the high levels of PPI during D1 and P. In contrast, when tested at a time of day in which PPI was low in D1 females, administration of both the typical antipsychotic drug haloperidol and the NT receptor antagonist significantly increased PPI. These data support an effect of time of day and estrous cycle stage on PPI in female rats. The estrous cycle variations in PPI are mediated in part by endogenous NT.
authors.affiliation: Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Suite 4000 WMRB, 101 Woodruff Circle, Atlanta, GA 30322, USA.
authors.forename: Becky
authors.initials: B
authors.lastname: Kinkead
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owens
authors.forename: Charles B
authors.initials: CB
authors.lastname: Nemeroff
mesh_terms: D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002940:Circadian Rhythm / Q000502:physiology; D004031:Diestrus / Q000378:metabolism*; D030762:Estrous Cycle / Q000378:metabolism; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D007266:Inhibition, Psychological; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009496:Neurotensin / Q000187:drug effects / Q000378:metabolism*; D011359:Proestrus / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D012737:Sex Factors; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C114947:SR 142948; D009496:Neurotensin; D006220:Haloperidol