Dopamine autoreceptor regulation of release and uptake in mouse brain slices in the absence of D3 receptors

Joseph, Joshua D.; Wang, Y.-M; Miles, Petrise Runnels; Budygin, Evgeny A.; Picetti, Roberto; Gainetdinov, Raul R.; Caron, Marc G.; Wightman, R. Mark

doi:10.1016/s0306-4522(02)00067-2

Cited by 149 publications

(146 citation statements)

References 53 publications

Supporting

Mentioning

131

Contrasting

Unclassified

Order By: Relevance

“…That is, in contrast to the D2R KO mice, mice lacking the DA D3R exhibited exaggerated cocaine-induced PPI deficits. One explanation could be that the elevated basal extracellular DA levels in D3 KO mice (Koeltzow et al, 1998;Joseph et al, 2002) could lead to the increased sensitivity to cocaine observed here in our D3 KO mice. There also seems to be opposing effects between the D1R and the D3R on the genomic effects of cocaine.…”

Section: Discussionmentioning

confidence: 89%

Contributions of Dopamine D1, D2, and D3 Receptor Subtypes to the Disruptive Effects of Cocaine on Prepulse Inhibition in Mice

Doherty

Masten

Powell

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

Deficits in prepulse inhibition (PPI) of startle, an operational measure of sensorimotor gating, are characteristics of schizophrenia and related neuropsychiatric disorders. Previous studies in mice demonstrate a contribution of dopamine (DA) D 1 -family receptors in modulating PPI and DA D 2 receptors (D2R) in mediating the PPI-disruptive effects of amphetamine. To examine further the contributions of DA receptor subtypes in PPI, we used a combined pharmacological and genetic approach. In congenic C57BL/6 J wildtype mice, we tested whether the D1R antagonist SCH23390 or the D2/3R antagonist raclopride would attenuate the effects of the indirect DA agonist cocaine (40 mg/kg). Both the D1R and D2/3R antagonists attenuated the cocaine-induced PPI deficit. We also tested the effect of cocaine on PPI in wild-type and DA D1R, D2R, or D3R knockout mice. The cocaine-induced PPI deficit was influenced differently by the three DA receptor subtypes, being absent in D1R knockout mice, partially attenuated in D2R knockout mice, and exaggerated in D3R knockout mice. Thus, the D1R is necessary for the PPI-disruptive effects of cocaine, while the D2R partially contributes to these effects. Conversely, the D3R appears to inhibit the PPI-disruptive effects of cocaine. Uncovering neural mechanisms involved in PPI will further our understanding of substrates of sensorimotor gating and could lead to better therapeutics to treat complex cognitive disorders such as schizophrenia.

show abstract

Section: Discussionmentioning

confidence: 89%

Contributions of Dopamine D1, D2, and D3 Receptor Subtypes to the Disruptive Effects of Cocaine on Prepulse Inhibition in Mice

Doherty

Masten

Powell

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…At the behavioral level, the originally described increased spontaneous locomotor activity exhibited by D3R mutant mice (Accili et al, 1996;Xu et al, 1997) has been replicated by some studies (Betancur et al, 2001;Boulay et al, 1999;Vallone et al, 2002) but not others (Joseph et al, 2002;Jung et al, 1999;McNamara et al, 2002). A significant increase in novelty-induced stereotypy has also been observed in D3R mutant mice relative to wild-type controls (Joseph et al, 2002).…”

Section: Introductionmentioning

confidence: 81%

“…Two studies using different D3R mutant mouse strains demonstrated that autoreceptor regulation of DA synthesis is intact in D3R knockout mice, while regulation of DA release is minimally impaired in D3R knockouts (Joseph et al, 2002;Koeltzow et al, 1998). Extracellular DA levels were elevated in the ventral striatum (Koeltzow et al, 1998) and caudate-putamen (Joseph et al, 2002) of D3R mutant mice relative to wildtype controls, suggesting some role for the D3R in the regulation of extracellular DA levels. In contrast, D2R knockout mice display complete loss of DA autoreceptor function (Mercuri et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…A significant increase in novelty-induced stereotypy has also been observed in D3R mutant mice relative to wild-type controls (Joseph et al, 2002). With regard to psychostimulant-induced locomotor activity, acute cocaineinduced locomotor activity was significantly greater in D3R mutant mice relative to wild-type mice at the lowest dose (5 mg/kg) tested; however, this effect was not observed at higher doses (10-40 mg/kg) (Xu et al, 1997).…”

Section: Introductionmentioning

confidence: 90%

See 1 more Smart Citation

Dose–response analysis of locomotor activity and stereotypy in dopamine D3 receptor mutant mice following acute amphetamine

McNamara

Logue

Stanford

et al. 2006

Synapse

View full text Add to dashboard Cite

Accumulating evidence suggests that dopamine D3 receptor (D3R) stimulation is inhibitory to spontaneous and psychostimulant-induced locomotion through opposition of concurrent D1R and D2R-mediated signaling. To evaluate this model, we used homozygous D3R mutant mice and wildtype controls to investigate the role of the D3R in locomotor activity and stereotypy stimulated by acute amphetamine (AMPH) (0.2, 2.5, 5.0, 10.0 mg/kg). At the lowest dose tested (0.2 mg/kg), neither D3R mutant mice nor wild-type mice exhibited measurable change in locomotor activity or stereotypy relative to their respective saline-treated controls. D3R mutant mice exhibited a significantly greater increase in locomotor activity, but not stereotypy, relative to wild-type mice in response to treatment with AMPH 2.5 mg/kg. AMPH-induced locomotor activity and stereotypy were similar in both wild-type and D3R mutant mice at both the 5.0 and 10 mg/kg AMPH doses. These findings provide further support for an inhibitory role for the D3R in AMPH-induced locomotor activity, and demonstrate a more limited role for the D3R in modulating AMPH-induced stereotypy.

show abstract

“…For example, D 3 blockade via antagonists or constitutive gene deletion induces hyperactivity (Accili et al, 1996;Waters et al, 1993) and D 3 agonists reduce activity (Daly and Waddington, 1993;Svensson et al, 1994). Additionally, D 3 KO mice have been reported to exhibit a 'hyperdopaminergic' phenotype, with increased striatal DA tone (Joseph et al, 2002;Koeltzow et al, 1998) and enhanced D 1 /D 2 intracellular signaling (Mizuo et al, 2004). Compensatory mechanisms such as reductions in tyrosine hydroxylase and increased DAT expression have been observed in D 3 KO mice (Le Foll et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Differential Contributions of Dopamine D1, D2, and D3 Receptors to MDMA-Induced Effects on Locomotor Behavior Patterns in Mice

Risbrough

Masten

Caldwell

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

MDMA or 'ecstasy' (3,4-methylenedioxymethamphetamine) is a commonly used psychoactive drug that has unusual and distinctive behavioral effects in both humans and animals. In rodents, MDMA administration produces a unique locomotor activity pattern, with high activity characterized by smooth locomotor paths and perseverative thigmotaxis. Although considerable evidence supports a major role for serotonin release in MDMA-induced locomotor activity, dopamine (DA) receptor antagonists have recently been shown to attenuate these effects. Here, we tested the hypothesis that DA D 1 , D 2 , and D 3 receptors contribute to MDMA-induced alterations in locomotor activity and motor patterns. DA D 1 , D 2 , or D 3 receptor knockout (KO) and wild-type (WT) mice received vehicle or ( + /À)-MDMA and were tested for 60 min in the behavioral pattern monitor (BPM). D 1 KO mice exhibited significant increases in MDMA-induced hyperactivity in the late testing phase as well as an overall increase in straight path movements. In contrast, D 2 KO mice exhibited reductions in MDMA-induced hyperactivity in the late testing phase, and exhibited significantly less sensitivity to MDMA-induced perseverative thigmotaxis. At baseline, D 2 KO mice also exhibited reduced activity and more circumscribed movements compared to WT mice. Female D 3 KO mice showed a slight reduction in MDMA-induced hyperactivity. These results confirm differential modulatory roles for D 1 and D 2 and perhaps D 3 receptors in MDMA-induced hyperactivity. More specifically, D 1 receptor activation appears to modify the type of activity (linear vs circumscribed), whereas D 2 receptor activation appears to contribute to the repetitive circling behavior produced by MDMA.

show abstract

Dopamine autoreceptor regulation of release and uptake in mouse brain slices in the absence of D3 receptors

Cited by 149 publications

References 53 publications

Contributions of Dopamine D1, D2, and D3 Receptor Subtypes to the Disruptive Effects of Cocaine on Prepulse Inhibition in Mice

Contributions of Dopamine D1, D2, and D3 Receptor Subtypes to the Disruptive Effects of Cocaine on Prepulse Inhibition in Mice

Dose–response analysis of locomotor activity and stereotypy in dopamine D3 receptor mutant mice following acute amphetamine

Differential Contributions of Dopamine D1, D2, and D3 Receptors to MDMA-Induced Effects on Locomotor Behavior Patterns in Mice

Contact Info

Product

Resources

About