title: Neonatal quinpirole treatment produces prepulse inhibition deficits in adult male and female rats.
abstract: We have shown that repeated neonatal quinpirole (QUIN; a dopamine D2-like receptor agonist) treatment in rats produces long-lasting supersensitization of dopamine D2 receptors that persists into adulthood but without producing a change in receptor number. The current study was designed to analyze the effects of neonatal QUIN on auditory sensorimotor gating as measured through prepulse inhibition (PPI). Male and female Sprague-Dawley rats were neonatally treated with QUIN (1mg/kg) or saline from postnatal days (P)1-21. At P60, the number of yawns was recorded for a 1h period in response to an acute QUIN (1mg/kg) injection as yawning is a D2-like receptor mediated behavioral event. Five days later, rats began (PPI) behavioral testing in two phases. In phase I, three different prepulse intensities (73, 76, and 82dB) were administered 100-ms before a 115dB pulse on 10 consecutive days. In phase II, three different interstimulus intervals (ISI; 50, 100, and 150ms) were inserted between the 73 or 76dB prepulse and 115dB pulse over 10 consecutive days of testing. A PPI probe trial was administered at the end of each phase after an acute 100μg/kgi.p. injection of QUIN to all animals. Replicating previous work, neonatal QUIN enhanced yawning compared to controls, verifying D2 receptor supersensitization. Regarding PPI, neonatal QUIN resulted in deficits across both phases of testing persistent across all testing days. Probe trial results revealed that acute QUIN treatment resulted in more robust PPI deficits in neonatal QUIN animals, although this deficit was related to prepulse intensity and ISI. These findings provide evidence that neonatal QUIN treatment results in deficits of auditory sensorimotor gating in adulthood as measured through PPI.
authors: Department of Basic Medical Sciences, The University of Arizona College of Medicine - Phoenix, 550 E. Van Buren St., Phoenix, AZ 85004, United States.
authors: Amanda M
authors: AM
authors: Maple
authors: Department of Psychology, East Tennessee State University, P. O. Box 70649, Johnson City, TN 37614, United States.
authors: Katherine J
authors: KJ
authors: Smith
authors: Department of Psychology, East Tennessee State University, P. O. Box 70649, Johnson City, TN 37614, United States.
authors: Marla K
authors: MK
authors: Perna
authors: Department of Psychology, East Tennessee State University, P. O. Box 70649, Johnson City, TN 37614, United States. Electronic address: brown1@mail.etsu.edu.
authors: Russell W
authors: RW
authors: Brown
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D018491:Dopamine Agonists / Q000633:toxicity*; D005260:Female; D008297:Male; D065808:Prepulse Inhibition / Q000187:drug effects* / Q000502:physiology; D019257:Quinpirole / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055139:Sensory Gating / Q000187:drug effects* / Q000502:physiology; D015000:Yawning / Q000187:drug effects* / Q000502:physiology
chemical_list: D018491:Dopamine Agonists; D019257:Quinpirole
keywords: Dopamine D2 receptor; Interstimulus interval; Neonatal quinpirole; Prepulse inhibition; Rats; Sensorimotor gating