Olfactory discrimination deficits in mice lacking the dopamine transporter or the D2 dopamine receptor.
Previous pharmacological studies have implicated dopamine as a modulator of olfactory bulb processing. Several disorders characterized by altered dopamine homeostasis in olfaction-related brain regions display olfactory deficits. To further characterize the role of dopamine in olfactory processing, we subjected dopamine transporter knockout mice (DAT -/-) and dopamine receptor 2 knockout mice (D2 -/-) to a battery of olfactory tests. In addition to behavioral characterization, several neurochemical markers of olfactory bulb integrity and function were examined. DAT -/- mice displayed an olfactory discrimination deficit, but did not differ detectably from DAT wildtype (DAT +/+) mice in odor habituation, olfactory sensitivity, or odor recognition memory. Neurochemically, DAT -/- mice have decreased D2 receptor staining in the periglomerular layer of the olfactory bulb and increased tyrosine hydroxylase immunoreactivity compared to DAT +/+ controls. D2 -/- mice exhibited the same olfactory deficit as the DAT -/- mice, further supporting the role of dopamine at the D2 synapse in olfactory discrimination processing. The findings presented in this paper reinforce the functional significance of dopamine and more specifically the D2 receptor in olfactory discrimination and may help explain the behavioral phenotype in the DAT and D2 knockout mice.
Tillerson
Jennifer L
JL
Center for Neurodegenerative Disease, Emory University, Atlanta, GA 30322, USA.
Caudle
W Michael
WM
Parent
Jack M
JM
Gong
C
C
Schallert
Timothy
T
Miller
Gary W
GW
D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D004193:Discrimination Learning; D004192:Discrimination, Psychological / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D006185:Habituation, Psychophysiologic / Q000502:physiology; D007150:Immunohistochemistry; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009830:Olfactory Bulb / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000502:physiology*; D012903:Smell / Q000502:physiology*
D000963:Antimetabolites; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; D001973:Bromodeoxyuridine