title: Parametric approaches towards understanding the effects of the preferential D3 receptor agonist pramipexole on prepulse inhibition in rats.
abstract: The preferential dopamine D3 receptor agonist pramipexole (PRA) disrupts prepulse inhibition (PPI) of acoustic startle, an operational measure of sensorimotor gating, in rats. Drug effects on PPI are sensitive to numerous experimental variables; proceeding with in-depth analyses of drug effects without a clear understanding of these variables is inefficient. The present studies characterized the impact on PRA-induced PPI deficits by a range of experimental parameters. As shown previously, PRA reduced both PPI and startle magnitude beginning 5-15 min post-injection; PRA effects on PPI were statistically significant through 35 min post-injection, while those on startle magnitude were still significant 65 min post-injection. PRA-induced PPI deficits were evident under conditions that matched startle magnitude in vehicle and PRA conditions and were independent of PRA-induced changes in prepulse-elicited motor activity. Additionally, PRA-induced PPI deficits did not differ significantly between uni- vs. cross-modal stimuli or between male vs. female rats, with no robust effect of estrous phase in females. These findings demonstrate that PRA effects on PPI are observed across several different experimental conditions and are dissociable from changes in startle magnitude or prepulse-elicited responses. Recommendations are made regarding "optimal" experimental conditions for studying the neurobiology of PRA-induced changes in PPI in rats.
authors.affiliation: Department of Psychiatry, UCSD School of Medicine, La Jolla, CA 92093-0804, USA.
authors.forename: Wei-li
authors.initials: WL
authors.lastname: Chang
authors.forename: Neal R
authors.initials: NR
authors.lastname: Swerdlow
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Breier
authors.forename: Niveditha
authors.initials: N
authors.lastname: Thangaraj
authors.forename: Martin
authors.initials: M
authors.lastname: Weber
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D030762:Estrous Cycle; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects*; D000077487:Pramipexole; D051381:Rats; D017207:Rats, Sprague-Dawley; D050637:Receptors, Dopamine D3 / Q000819:agonists*; D013216:Reflex, Startle / Q000187:drug effects; D055139:Sensory Gating / Q000187:drug effects; D012727:Sex Characteristics; D013997:Time Factors
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D050637:Receptors, Dopamine D3; D000077487:Pramipexole
references.citation: Arch Gen Psychiatry. 1992 Mar;49(3):206-15
references.pmid: 1567275
references.citation: Psychoneuroendocrinology. 2008 Feb;33(2):178-87
references.pmid: 18155361
references.citation: Psychopharmacology (Berl). 1999 Sep;146(2):228-32
references.pmid: 10525760
references.citation: Psychopharmacology (Berl). 2009 Sep;205(4):689-98
references.pmid: 19506839
references.citation: J Neurosci. 1995 Mar;15(3 Pt 2):2301-11
references.pmid: 7891168
references.citation: Psychopharmacology (Berl). 2008 Aug;199(3):331-88
references.pmid: 18568339
references.citation: Biol Psychiatry. 1996 Jan 1;39(1):33-41
references.pmid: 8719124
references.citation: Psychopharmacology (Berl). 1990;102(1):1-4
references.pmid: 2392496
references.citation: Biol Psychiatry. 2001 Oct 15;50(8):578-85
references.pmid: 11690592
references.citation: Behav Neurosci. 2000 Apr;114(2):374-88
references.pmid: 10832798
references.citation: Psychopharmacology (Berl). 2004 Aug;174(4):452-62
references.pmid: 15300359
references.citation: Behav Pharmacol. 2005 Mar;16(2):127-30
references.pmid: 15767849
references.citation: Physiol Behav. 1998 Jul;64(5):625-8
references.pmid: 9817573
references.citation: Behav Brain Res. 1999 Oct;104(1-2):113-7
references.pmid: 11125729
references.citation: J Pharmacol Exp Ther. 2002 Nov;303(2):791-804
references.pmid: 12388666
references.citation: Neurosci Lett. 1996 Nov 22;219(2):138-40
references.pmid: 8971799
references.citation: Eur J Pharmacol. 1994 Oct 3;263(3):235-43
references.pmid: 7843260
references.citation: Pharmacol Biochem Behav. 2008 Jan;88(3):280-90
references.pmid: 17936348
references.citation: Behav Brain Res. 2009 Dec 7;204(2):387-95
references.pmid: 19114060
references.citation: Psychopharmacology (Berl). 1988;95(2):151-6
references.pmid: 3137590
references.citation: Behav Brain Res. 2009 Jun 8;200(1):165-72
references.pmid: 19373982
references.citation: Psychopharmacology (Berl). 1988;94(4):507-14
references.pmid: 3131796
references.citation: Braz J Biol. 2002 Nov;62(4A):609-14
references.pmid: 12659010
references.citation: J Neurosci. 1999 Jul 1;19(13):5644-53
references.pmid: 10377370
references.citation: Pharmacol Biochem Behav. 2009 Aug;93(2):141-7
references.pmid: 19426754
references.citation: Pharmacol Biochem Behav. 2008 Jan;88(3):306-11
references.pmid: 17900675
references.citation: Behav Pharmacol. 2008 Dec;19(8):786-95
references.pmid: 19020413
references.citation: J Neurosci Methods. 2008 Aug 30;173(2):295-8
references.pmid: 18621080
references.citation: Neuropsychopharmacology. 1998 Jan;18(1):50-6
references.pmid: 9408918