Abstract:
:Dopamine (DA) D2 receptors expressed in DA neurons (D2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. As D2 receptors are mostly expressed in postsynaptic neurons, pharmacological and genetic approaches have been unable to definitively address the in vivo contribution of D2 autoreceptors to DA-mediated behaviors. We found that midbrain DA neurons from mice deficient in D2 autoreceptors (Drd2(loxP/loxP); Dat(+/IRES-cre), referred to as autoDrd2KO mice) lacked DA-mediated somatodendritic synaptic responses and inhibition of DA release. AutoDrd2KO mice displayed elevated DA synthesis and release, hyperlocomotion and supersensitivity to the psychomotor effects of cocaine. The mice also exhibited increased place preference for cocaine and enhanced motivation for food reward. Our results highlight the importance of D2 autoreceptors in the regulation of DA neurotransmission and demonstrate that D2 autoreceptors are important for normal motor function, food-seeking behavior, and sensitivity to the locomotor and rewarding properties of cocaine.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Bello EP,Mateo Y,Gelman DM,Noaín D,Shin JH,Low MJ,Alvarez VA,Lovinger DM,Rubinstein Mdoi
10.1038/nn.2862subject
Has Abstractpub_date
2011-07-10 00:00:00pages
1033-8issue
8eissn
1097-6256issn
1546-1726pii
nn.2862journal_volume
14pub_type
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