Impaired light masking in dopamine D2 receptor–null mice

Abstract

Disruption of overt circadian rhythms can occur without influencing the endogenous pacemaker, the so-called 'masking' effect classically elicited by light. As the physiological pathways involved in light masking remain elusive, we analyzed mice lacking the dopamine D2 receptor. Although circadian rhythmicity was normal, D2R-null mice showed a markedly deficient light masking response, indicating that D2R-mediated signaling is an essential component of the neuronal pathways leading to light masking of circadian rhythms.

Essential Role of Dopamine D2Receptor in the Maintenance of Wakefulness, But Not in Homeostatic Regulation of Sleep, in Mice

“…D 2 R KO mice exhibited a significant decrease in wakefulness concomitant with an increase in NREM and REM sleep under baseline conditions, which is consistent with an apparent reduction in the spontaneous locomotor activity previously reported to occur in these mice (Kelly et al, 1998;Doi et al, 2006). D 2 R KO mice sleep longer than WT mice, exhibit NREM delta power lower than that of WT mice, and frequently enter sleep after short periods of wakefulness, indicating that D 2 R KO mice have poor quality of NREM sleep.…”

Dopaminergic D1and D2Receptors Are Essential for the Arousal Effect of Modafinil

“…3) but with an increase in NREM sleep during dark periods (data not shown). Although circadian rhythmicity was normal, D 2 R KO mice showed a markedly deficient light-masking response, indicating that D 2 R-mediated signaling is an essential component of the neuronal pathways leading to light masking of circadian rhythms (Doi et al, 2006).…”

The Physiology, Signaling, and Pharmacology of Dopamine Receptors

“…In contrast, the specific ablation of DARPP-32 in neurons that express D2 dopamine receptors resulted in enhanced locomotor responses to cocaine and an enhanced level of basal locomotor activity (Bateup et al, 2010). This latter observation is interesting because mice lacking D2 dopamine receptors or the predominantly postsynaptic D2L variant have been shown to display an overall reduction in basal locomotor activity and in their responsiveness to cocaine (Baik et al, 1995;Vargas-Pérez et al, 2004;Doi et al, 2006;Welter et al, 2007). These findings suggest that a reduction in phospho-threonine 34 DARPP-32 in response to D2 dopamine receptor stimulation may contribute to some of the pro-locomotor effects that are associated with D2 dopamine receptor activation.…”