Pharmacological blockade and genetic absence of the dopamine D2 receptor specifically modulate voluntary locomotor activity in mice

Klinker, Florian; Hasan, Kenan; Paulus, Walter; Nitsche, Michael A.; Liebetanz, David

doi:10.1016/j.bbr.2012.12.038

Cited by 20 publications

(15 citation statements)

References 28 publications

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“…Thus, Experiment 2 examined whether wheel running reduces preference for a previously preferred HF diet. Both the dopaminergic and opioid systems mediate the intensity/amount (Boer et al, 1990, Sisti and Lewis, 2001, Knab et al, 2012, Roberts et al, 2012, Klinker et al, 2013) as well as the rewarding effects of wheel running in rodents (Lett et al, 2001, Vargas-Perez et al, 2008, Greenwood et al, 2011, Rasmussen and Hillman, 2011). Thus, Experiment 2 also determined whether wheel running alters the mRNA expression of dopaminergic and opioidergic genes in reward pathways.…”

Section: Introductionmentioning

confidence: 99%

Wheel running reduces high-fat diet intake, preference and mu-opioid agonist stimulated intake

Liang

Bello

Moran

2015

Behavioural Brain Research

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The ranges of mechanisms by which exercise affects energy balance remain unclear. One potential mechanism may be that exercise reduces intake and preference for highly palatable, energy dense fatty foods. The current study used a rodent wheel running model to determine whether and how physical activity affects HF diet intake/preference and reward signaling. Experiment 1 examined whether wheel running affected the ability of intracerebroventricular (ICV) µ opioid receptor agonist D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO) to increase HF diet intake. Experiment 2 examined the effects of wheel running on the intake of and preference for a previously preferred HF diet. We also assessed the effects of wheel running and diet choice on mesolimbic dopaminergic and opioidergic gene expression. Experiment 1 revealed that wheel running decreased the ability of ICV DAMGO administration to stimulate HF diet intake. Experiment 2 showed that wheel running suppressed weight gain and reduced intake and preference for a previously preferred HF diet. Furthermore, the mesolimbic gene expression profile of wheel running rats was different from that of their sedentary paired-fed controls but similar to that of sedentary rats with large HF diet consumption. These data suggest that alterations in preference for palatable, energy dense foods play a role in the effects of exercise on energy homeostasis. The gene expression results also suggest that the hedonic effects of exercise may substitute for food reward to limit food intake and suppress weight gain.

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Section: Introductionmentioning

confidence: 99%

Wheel running reduces high-fat diet intake, preference and mu-opioid agonist stimulated intake

Liang

Bello

Moran

2015

Behavioural Brain Research

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“…NTS1 is thought to inhibit dopamine transmission through an interaction with dopamine D2 receptors (D2R) (Binder et al, 2001). D2R activity appears to be positively correlated with locomotor activity given that D2R KO mice are hypoactive and D2R antagonists suppress locomotion (Kelly et al, 1998; Klinker et al, 2013). Therefore, one mechanism by which NT may reduce locomotor activity could be through inhibition of D2R function.…”

Section: Introductionmentioning

confidence: 99%

Activation of neurotensin receptor type 1 attenuates locomotor activity

et al. 2014

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Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders.

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“…rats (Meyer and Shults 1993;Klinker et al 2013). In mammals, dopamine receptors are coupled to Gproteins and are classified as either D1-like or D2-like based on their downstream signalling.…”

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confidence: 99%

Differential effects of dopamine D1 and D2/3 receptor antagonism on motor responses

et al. 2014

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Pharmacological blockade and genetic absence of the dopamine D2 receptor specifically modulate voluntary locomotor activity in mice

Cited by 20 publications

References 28 publications

Wheel running reduces high-fat diet intake, preference and mu-opioid agonist stimulated intake

Wheel running reduces high-fat diet intake, preference and mu-opioid agonist stimulated intake

Activation of neurotensin receptor type 1 attenuates locomotor activity

Differential effects of dopamine D1 and D2/3 receptor antagonism on motor responses

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