Social odor recognition: a novel behavioral model for cognitive dysfunction in Parkinson's disease.
BACKGROUND
Parkinson's disease (PD) is a progressive neurodegenerative condition characterized by an increasing loss of dopaminergic neurons resulting in motor dysfunction. However, cognitive impairments in PD patients are a common clinical feature that has gained increased attention.


OBJECTIVE
The purpose of the current study was to evaluate the effects of an MPTP-induced dopaminergic lesion in mice on social odor recognition (SOR) memory.


METHODS
Mice were acutely treated with MPTP and evaluated for memory impairments in the SOR assay and characterized using biochemical and immunohistochemical methods approximately 2 weeks later.


RESULTS
Here we demonstrate that SOR memory is sensitive to MPTP treatment and that it correlates with multiple measures of nigrostriatal integrity. MPTP treatment of C57BL/6N mice produced a profound decrease in dopamine levels, dopamine transporter binding and tyrosine hydroxylase immunoreactivity in the striatum. These impairments in stratial dopaminergic function were blocked by pretreatment with the MAO-B inhibitor deprenyl. Changes in the dopaminergic system parallel those observed in SOR with MPTP treatment impairing recognition memory in the absence of a deficit in odor discrimination during learning. Deprenyl pretreatment blocked the MPTP-induced impairment of SOR memory.


CONCLUSIONS
The use of the SOR memory model may provide a preclinical method for evaluating cognitive therapies for PD.
Monaghan
Michael M
MM
Discovery Neuroscience, Pfizer Global Research and Development, CN8000, Princeton, NJ 08534, USA. monaghm@wyeth.com
Leddy
Lauren
L
Sung
Mei-Li Amy
ML
Albinson
Kristin
K
Kubek
Katie
K
Pangalos
Menelas N
MN
Reinhart
Peter H
PH
Zaleska
Margaret M
MM
Comery
Thomas A
TA
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D020267:MPTP Poisoning / Q000139:chemically induced / Q000150:complications* / Q000473:pathology / Q000523:psychology*; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D021641:Recognition, Psychology / Q000502:physiology*; D012930:Social Dominance; D013378:Substantia Nigra / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine