VGLUT2 in dopamine neurons is required for psychostimulant-induced behavioral activation.
The "One neuron-one neurotransmitter" concept has been challenged frequently during the last three decades, and the coexistence of neurotransmitters in individual neurons is now regarded as a common phenomenon. The functional significance of neurotransmitter coexistence is, however, less well understood. Several studies have shown that a subpopulation of dopamine (DA) neurons in the ventral tegmental area (VTA) expresses the vesicular glutamate transporter 2 (VGLUT2) and has been suggested to use glutamate as a cotransmitter. The VTA dopamine neurons project to limbic structures including the nucleus accumbens, and are involved in mediating the motivational and locomotor activating effects of psychostimulants. To determine the functional role of glutamate cotransmission by these neurons, we deleted VGLUT2 in DA neurons by using a conditional gene-targeting approach in mice. A DAT-Cre/Vglut2Lox mouse line (Vglut2(f/f;DAT-Cre) mice) was produced and analyzed by in vivo amperometry as well as by several behavioral paradigms. Although basal motor function was normal in the Vglut2(f/f;DAT-Cre) mice, their risk-taking behavior was altered. Interestingly, in both home-cage and novel environments, the gene targeted mice showed a greatly blunted locomotor response to the psychostimulant amphetamine, which acts via the midbrain DA system. Our results show that VGLUT2 expression in DA neurons is required for normal emotional reactivity as well as for psychostimulant-mediated behavioral activation.
Birgner
Carolina
C
Unit of Developmental Genetics, Department of Neuroscience, Uppsala University, S-751 24 Uppsala, Sweden.
Nordenankar
Karin
K
Lundblad
Martin
M
Mendez
José Alfredo
JA
Smith
Casey
C
le Grevès
Madeleine
M
Galter
Dagmar
D
Olson
Lars
L
Fredriksson
Anders
A
Trudeau
Louis-Eric
LE
Kullander
Klas
K
Wallén-Mackenzie
Asa
A
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D012309:Risk-Taking; D012737:Sex Factors; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics / Q000378:metabolism*
D000697:Central Nervous System Stimulants; D050599:Vesicular Glutamate Transport Protein 2; D018698:Glutamic Acid; D000661:Amphetamine; D004298:Dopamine