Acoustic startle response, prepulse inhibition, and spontaneous locomotor activity in MPTP-treated mice.
Parkinson's disease (PD) is marked by characterised motor deficits and is accompanied by a severe degeneration of the nigrostriatal dopamine (DA) pathway. It has also been reported that PD patients exhibited additional behavioural deficits, including a deficiency in sensorimotor gating mechanisms. We therefore examined whether the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD in mice could lead to a sensorimotor gating deficit in the prepulse inhibition (PPI) of the acoustic startle response (ASR) paradigm. Two MPTP treatment schedules were separately examined here in male C57BL/6 mice. Post-mortem HPLC analysis confirmed that they were effective in depleting DA in the dorsal striatum (75-88%). PPI was evaluated on days 2, 9 and 16 after the last MPTP treatment; spontaneous locomotor activity was assessed 24 h before each PPI test. No significant change in the expression of PPI was detected across the three time points. On the other hand, the MPTP treatment reduced activity on post-treatment day 1. This effect subsided on post-treatment day 8, and was reversed on day 15. The possibility remains therefore that the reported sensorimotor gating deficits in PD patients might stem from structural or neurochemical aberrations beyond those induced by MPTP treatment.
Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland.
Andreas
A
Leng
Benjamin K
BK
Yee
Joram
J
Feldon
Boris
B
Ferger
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D004334:Drug Administration Schedule; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D009433:Neural Inhibition / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D012022:Reflex, Acoustic / Q000187:drug effects*; D013997:Time Factors
D015259:Dopamine Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid