Dopamine D2 receptor knock-out mice are insensitive to the hypolocomotor and hypothermic effects of dopamine D2/D3 receptor agonists

Boulay, Denis; Depoortère, R.; Perrault, Ghislaine; Borrelli, Emiliana; Sanger, D. J.

doi:10.1016/s0028-3908(99)00064-7

Cited by 96 publications

(60 citation statements)

References 26 publications

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“…The phenotype for the D 2 knockout line of Baik et al (1995) was characterised over initial exploration by modest but significant reductions in locomotion, grooming, rearing free and rearing to wall; rearing seated, sniffing, sifting and stillness were not altered. Individual elements of behaviour habituated similarly over a 6-h period for both genotypes, in the face of essential abolition of responsivity to D 2 -like agonism; in contrast to the original report of Baik et al (1995), we could not identify a prominence of 'parkinsonian-like' or other neurological components to the ethogram using these procedures , as recently noted also by others using an alternative behavioural approach (Boulay et al 1999a(Boulay et al , 2000.…”

contrasting

confidence: 93%

Comparative, Topographically-Based Evaluation of Behavioural Phenotype and Specification of D1-Like:D2 Interactions in a Line of Incipient Congenic Mice with D2 Dopamine Receptor 'Knockout'

Clifford

Kinsella²,

Tighe

et al. 2001

Neuropsychopharmacology

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contrasting

confidence: 93%

Comparative, Topographically-Based Evaluation of Behavioural Phenotype and Specification of D1-Like:D2 Interactions in a Line of Incipient Congenic Mice with D2 Dopamine Receptor 'Knockout'

Clifford

Kinsella²,

Tighe

et al. 2001

Neuropsychopharmacology

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“…On the contrary, some studies in mice reported a reduction of motor activity after i.p. injection of low doses of quinelorane (Boulay et al, 1999;Frances et al, 2001). Motor activity has not been measured but even if quinelorane induced some hypoactivity in the present experimental conditions, the enhancement of food-primed response reinstatement occurred despite this effect and in no case can be accounted for by this effect.…”

Section: Discussioncontrasting

confidence: 55%

Blockade by the Cannabinoid CB1 Receptor Antagonist, Rimonabant (SR141716), of the Potentiation by Quinelorane of Food-Primed Reinstatement of Food-Seeking Behavior

Duarte

Alonso

Bichet

et al. 2003

Neuropsychopharmacol

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It has been shown previously that the selective cannabinoid CB1 receptor antagonist, rimonabant (SR141716), reduced the intake of palatable food as well as the self-administration of several drugs of abuse, suggesting that endocannabinoid systems play a role in brain reward function. The present study investigated whether a cannabinoid step was involved in food-seeking behavior induced by explicit stimuli, using an operant reinstatement procedure in rats. Experimental sessions consisted of a 15-min food rewarded period, followed by a 45-min extinction period. Rimonabant did not affect the response reinstatement induced by noncontingent delivery of food pellets, but prevented (0.03-0.3 mg/kg) the potentiation by quinelorane, a dopamine D3 receptor-preferring agonist, of food-seeking behavior. A possible link between cannabinoid processes and D3-and/or D2-mediated dopaminergic transmission was further investigated by studying Fos protein expression in cortico-limbic structures in D3 (D3À/À) and D2 (D2À/À) knockout mice. Rimonabant (10 mg/kg) increased Fos immunoreactivity in the prefrontal cortex (pFCortex) and in the shell but not the core of the nucleus accumbens (NAcc). Fos induction by this dose of rimonabant was not seen in mice lacking CB1 receptors, providing clear evidence for the involvement of CB1 receptors. In the NAcc shell, the effect of rimonabant was suppressed in D3À/À, but remained unchanged in D2À/À mice. In contrast, Fos expression by rimonabant in the pFCortex was impervious to D2 or D3 receptor deletion. In conclusion, these data indicate first that rimonabant prevented the enhancement by quinelorane of the appetitive value of food pellets unexpectedly delivered during extinction and second that rimonabant effects might involve D3 receptor-mediated processes. Overall, these results are consistent with the notion that endocannabinoid functions control brain reward processes and in particular the capacity of explicit stimuli to precipitate food-seeking behavior.

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“…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: 82%

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

McNamara

Logue

Stanford

et al. 2006

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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.

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Dopamine D2 receptor knock-out mice are insensitive to the hypolocomotor and hypothermic effects of dopamine D2/D3 receptor agonists

Cited by 96 publications

References 26 publications

Comparative, Topographically-Based Evaluation of Behavioural Phenotype and Specification of D1-Like:D2 Interactions in a Line of Incipient Congenic Mice with D2 Dopamine Receptor 'Knockout'

Comparative, Topographically-Based Evaluation of Behavioural Phenotype and Specification of D1-Like:D2 Interactions in a Line of Incipient Congenic Mice with D2 Dopamine Receptor 'Knockout'

Blockade by the Cannabinoid CB1 Receptor Antagonist, Rimonabant (SR141716), of the Potentiation by Quinelorane of Food-Primed Reinstatement of Food-Seeking Behavior

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

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