Dopamine D2 Receptor Overexpression Alters Behavior and Physiology in<i>Drd2-EGFP</i>Mice

Kramer, P.; Christensen, Christine H.; Hazelwood, Lisa A; Dobi, Alice; Bock, Roland; Sibley, David R.; Mateo, Yolanda; Alvarez, Veronica A.

doi:10.1523/jneurosci.4287-10.2011

Cited by 99 publications

(102 citation statements)

References 25 publications

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“…Several groups have reported alterations of DA transmission in certain BAC lines (Bagetta et al, 2012;Kramer et al, 2011); therefore, we measured brain tissue DA to ascertain whether our mouse model was normal or deficient in this respect. Importantly, we found no differences in the levels of DA or its metabolites in the caudate-putamen/nucleus accumbens region or the prefrontal cortex between the Th-EGFP mice and their littermates without the transgene.…”

Section: Gan-induced Glutamate Receptor Plasticitymentioning

confidence: 99%

Neurosteroid Agonist at GABAA Receptor Induces Persistent Neuroplasticity in VTA Dopamine Neurons

Vashchinkina

Manner

Vekovischeva

et al. 2013

Neuropsychopharmacol

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The main fast-acting inhibitory receptors in the mammalian brain are g-aminobutyric acid type-A (GABA A ) receptors for which neurosteroids, a subclass of steroids synthesized de novo in the brain, constitute a group of endogenous ligands with the most potent positive modulatory actions known. Neurosteroids can act on all subtypes of GABA A receptors, with a preference for d-subunitcontaining receptors that mediate extrasynaptic tonic inhibition. Pathological conditions characterized by emotional and motivational disturbances are often associated with perturbation in the levels of endogenous neurosteroids. We studied the effects of ganaxolone (GAN)-a synthetic analog of endogenous allopregnanolone that lacks activity on nuclear steroid receptors-on the mesolimbic dopamine (DA) system involved in emotions and motivation. A single dose of GAN in young mice induced a dose-dependent, longlasting neuroplasticity of glutamate synapses of DA neurons ex vivo in the ventral tegmental area (VTA). Increased a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/N-methyl-D-aspartate ratio and rectification of AMPA receptor responses even at 6 days after GAN administration suggested persistent synaptic targeting of GluA2-lacking AMPA receptors. This glutamate neuroplasticity was not observed in GABA A receptor d-subunit-knockout (d-KO) mice. GAN (500 nM) applied locally to VTA selectively increased tonic inhibition of GABA interneurons and triggered potentiation of DA neurons within 4 h in vitro. Place-conditioning experiments in adult wild-type C57BL/6J and d-KO mice revealed aversive properties of repeated GAN administration that were dependent on the d-subunits. Prolonged neuroadaptation to neurosteroids in the VTA might contribute to both the physiology and pathophysiology underlying processes and changes in motivation, mood, cognition, and drug addiction.

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Section: Gan-induced Glutamate Receptor Plasticitymentioning

confidence: 99%

Neurosteroid Agonist at GABAA Receptor Induces Persistent Neuroplasticity in VTA Dopamine Neurons

Vashchinkina

Manner

Vekovischeva

et al. 2013

Neuropsychopharmacol

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“…Recent studies have reported several behavioral and physiological alterations in drd2-eGFP mice (Kramer et al, 2011) that could influence opioid withdrawal. (Fig.…”

Section: Naloxone-precipitated Opioid Withdrawal Induces C-fos Expresmentioning

confidence: 99%

Nucleus accumbens D2- and D1-receptor expressing medium spiny neurons are selectively activated by morphine withdrawal and acute morphine, respectively

2012

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“…Nevertheless, caution in the interpretation of data resulting from the use of eGFP transgenic mice is needed since it has been indeed recently reported that D 2 R-eGFP mice express an altered behavioral and physiological phenotype due to D 2 receptor overexpression (Kramer et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Dopamine-Dependent Long-Term Depression Is Expressed in Striatal Spiny Neurons of Both Direct and Indirect Pathways: Implications for Parkinson's Disease

Bagetta¹,

Picconi²,

Marinucci³

et al. 2011

J. Neurosci.

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Striatal medium spiny neurons (MSNs) are divided into two subpopulations exerting distinct effects on motor behavior. Transgenic mice carrying bacterial artificial chromosome (BAC) able to confer cell type-specific expression of enhanced green fluorescent protein (eGFP) for dopamine (DA) receptors have been developed to characterize differences between these subpopulations. Analysis of these mice, in contrast with original pioneering studies, showed that striatal long-term depression (LTD) was expressed in indirect but not in the direct pathway MSNs. To address this mismatch, we applied a new approach using combined BAC technology and receptor immunohistochemistry. We demonstrate that, in physiological conditions, DA-dependent LTD is expressed in both pathways showing that the lack of synaptic plasticity found in D 1 eGFP mice is associated to behavioral deficits. Our findings suggest caution in the use of this tool and indicate that the "striatal segregation" hypothesis might not explain all synaptic dysfunctions in Parkinson's disease.

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Dopamine D2 Receptor Overexpression Alters Behavior and Physiology inDrd2-EGFPMice

Cited by 99 publications

References 25 publications

Neurosteroid Agonist at GABAA Receptor Induces Persistent Neuroplasticity in VTA Dopamine Neurons

Neurosteroid Agonist at GABAA Receptor Induces Persistent Neuroplasticity in VTA Dopamine Neurons

Nucleus accumbens D2- and D1-receptor expressing medium spiny neurons are selectively activated by morphine withdrawal and acute morphine, respectively

Dopamine-Dependent Long-Term Depression Is Expressed in Striatal Spiny Neurons of Both Direct and Indirect Pathways: Implications for Parkinson's Disease

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