D1 receptors mediate dopamine action in the fetal suprachiasmatic nuclei: studies of mice with targeted deletion of the D1 dopamine receptor gene

Bender, Mark; Drago, John; Rivkees, Scott A.

doi:10.1016/s0169-328x(97)00161-7

Cited by 23 publications

(29 citation statements)

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“…D 1 -R mRNA has been described in the SCN of other altricial rodents, including the foetal and adult rat and the foetal Syrian hamster (Weaver et al, 1992;Viswanathan et al, 1994). It would appear that the D 1 -R mRNA is translated, because immunocytochemical and radioligand binding studies have detected D 1 -R in the foetal and adult rodent SCN (Juhasz et al, 1987;Huang et al, 1992;Bender et al, 1997;Shearman et al, 1997;Strother et al, 1998a). A recent study has also revealed D 1 -R mRNA and functional receptor in the foetal and adult primate, including the human (Rivkees and Lachowicz, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…SKF 81297 is a full agonist and a more potent drug than SKF 38393, as assessed by its greater efficacy of cyclic AMP (cAMP) activation and comparable behavioural effects at lower doses (Murray and Waddington, 1989;Andersen and Jansen, 1990;Arnt et al, 1992). SKF 38393 is a partial agonist and has been used commonly to investigate D 1 -R-mediated responses of the neonatal rodent SCN (Weaver et al, 1992Viswanathan et al, 1994;Bender et al, 1997;Viswanathan and Davis, 1997), whereas N-allyl-SKF 38393 has been shown to be particularly lipophilic, thus potentially increasing the permeability of the agonist into the tissue block and transport across the blood-brain barrier (Self and Stein, 1992). SKF 81297 was used at 5 mg/kg, because this dose results in a consistent enhancement of locomotor activity and induction of c-fos expression within the caudate putamen in studies of adult Siberian hamsters .…”

Section: -Dopamine Receptor Agonistsmentioning

confidence: 99%

“…More recently, a role for a dopaminergic system has been implicated in transducing maternal signals in the foetal brain. The foetal SCN in the rat, mouse, and Syrian hamster express the gene for D 1 -dopamine receptor (D 1 -R), and treatment with cocaine or D 1 -R agonist is capable of inducing the expression of c-fos within the foetal rodent SCN (Weaver et al, 1992Viswanathan et al, 1994;Bender et al, 1997). It is noteworthy that recent studies have revealed mRNA and functional D 1 -R, localised by radioligand binding, within the foetal and adult SCN of the primate, including the human (Rivkees and Lachowicz, 1997).…”

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confidence: 99%

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Anatomical and functional characterisation of a dopaminergic system in the suprachiasmatic nucleus of the neonatal siberian hamster

1999

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In altricial rodents, maternal influences entrain the developing circadian system in the perinatal period before the capacity to respond directly to photic cues develops. The aim of these studies was to investigate the potential role of dopamine in this process in the Siberian hamster. An initial study investigated the ontogeny of retinal innervation of the suprachiasmatic nuclei (SCN) by using cholera toxin B subunit as a tracer. This revealed that retinal fibres first innervate the SCN on postnatal day 3 (PD3), and ingrowth of fibres is extensive by PD6. In situ hybridisation studies revealed the presence of D1‐dopamine receptor (D1‐R) mRNA in the SCN on PD2, and levels of expression were similar in PD6 pups and adult hamsters. Immunocytochemical staining for tyrosine hydroxylase revealed abundant catecholaminergic fibres within the ventromedial zone of the SCN from the day of birth through PD20; however, in contrast, few fibres were present in adult SCN. Dopamine‐β‐hydroxylase‐immunoreactive fibres were absent from the neonatal and adult SCN, suggesting that the fibres in the SCN are dopaminergic. The function of this dopaminergic system was investigated by determining the effects of D1‐R agonists on the expression of the immediate‐early gene c‐fos in the SCN. This was assessed in pups ages PD1– PD5 by in situ hybridisation and immunocytochemical localisation of its protein product. No induction was seen in the SCN, in marked contrast to studies in the developing rat. A final series of studies investigated dopaminergic function by determining whether a D1‐agonist could induce phosphorylation of Ca2+/cyclic AMP response element‐binding protein (CREB) on Ser133. Hypothalamic slices containing SCN taken from PD1 and PD2 hamsters were treated with D1‐R agonists, and levels of phosphorylated CREB were assayed by Western blots. Phosphorylation of CREB was stimulated by D1‐R agonists in both Syrian and Siberian hamster hypothalamus, but the response was far greater in Syrian hamster tissue (+138% ± 28%) than in Siberian hamster tissue (+43% ± 11%). Although the anatomical studies demonstrate the existence of a dopaminergic system in the SCN of the early postnatal Siberian hamster, the unresponsiveness of c‐fos expression and the relative lack of phosphorylation of CREB after D1‐R activation suggests a diminished role for dopamine in the regulation of circadian events during the postnatal period in this species. J. Comp. Neurol. 408:73–96, 1999. © 1999 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Section: -Dopamine Receptor Agonistsmentioning

confidence: 99%

mentioning

confidence: 99%

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Anatomical and functional characterisation of a dopaminergic system in the suprachiasmatic nucleus of the neonatal siberian hamster

1999

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“…In mammals, dopamine is an important component of the input pathway to the pacemaker during a restricted phase of development (48)(49)(50). Dopamine, acting through a D1 receptor that is highly expressed before birth, conveys nonphotic information mediating maternal-fetal entrainment (48,49).…”

Section: Partial Autonomy Of the Nerve Cord Oscillators Controlling Dmentioning

confidence: 99%

“…Dopamine, acting through a D1 receptor that is highly expressed before birth, conveys nonphotic information mediating maternal-fetal entrainment (48,49). D1 receptors continue to be expressed in the adult circadian pacemaker; however, they do not seem to play a role in photic control, a major form of entrainment of the adult circadian clock (50).…”

Section: Partial Autonomy Of the Nerve Cord Oscillators Controlling Dmentioning

confidence: 99%

Circadian modulation of dopamine receptor responsiveness in Drosophila melanogaster

Andretic

Hirsh

2000

Proc. Natl. Acad. Sci. U.S.A.

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We investigated the circadian function of Drosophila dopamine receptors by using a behaviorally active decapitated preparation that allows for direct application of drugs to the nerve cord. Quinpirole, a D2-like dopamine receptor agonist, induces reflexive locomotion in decapitated flies. We show that the amount of locomotion induced changes as a function of the time of day, with the highest responsiveness to quinpirole during the subjective night. Furthermore, dopamine receptor responsiveness is under circadian control and depends on the normal function of the period gene. The head pacemaker is at least partly dispensable for the circadian modulation of quinpirole-induced locomotion, because changes in agonist responsiveness persist in decapitated flies that are aged for 12 h. This finding suggests a role for the perioddependent molecular oscillators in the body in the modulation of amine receptor responsiveness. Circadian rhythms are genetically determined biological oscillations with a period of close to 24 h evident in the physiology and behavior of most organisms (1, 2). One of the most obvious behaviors controlled by the circadian pacemaker in a variety of organisms is the rest-activity cycle, which can be clearly seen in Drosophila (3, 4). Components of the circadian pacemaker responsible for rhythm generation were first identified in Drosophila, but recent data from other organisms, including humans, indicate a conservation in the molecular mechanisms underlying circadian rhythms (5-10).The first genetically identified circadian mutant, period (per), encodes one of the essential elements involved in the transcription͞translation-based autoregulatory loop of the cellular circadian pacemaker (3, 6). In Drosophila, the role of per in a group of brain neurons, the lateral neurons, is essential for the expression of circadian locomotor rhythm, thus pointing to these neurons as the site of the circadian pacemaker (11-14). However, studies in Drosophila indicate that circadian rhythm generators are not exclusively neural. In flies, per expression is also present in nonneural tissues, such as the Malpighian tubules, gut, testes, ovaries, and the chemosensory cells of the antennae (15-18). Most of these cells appear to contain autonomous per-based circadian oscillators (16), but only in the case of the antennal chemosensory cells have these peripheral oscillators been linked to a functional output (18).Control of motor behaviors in both vertebrates and invertebrates has been linked to the biogenic amines, found in the central and peripheral nervous system (19-23). Dopamine receptors with greatest similarity to the mammalian D1-like Gprotein-coupled receptors have been cloned in Drosophila (24-27). Although a D2-like dopamine receptor has not been identified at the molecular level in Drosophila or other insects, several lines of evidence support its existence (28-30).Our laboratory has described a behaviorally active preparation of decapitated Drosophila that allows for direct application of drugs to the nerve cor...

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Anatomical and functional characterisation of a dopaminergic system in the suprachiasmatic nucleus of the neonatal siberian hamster

Duffield¹,

McNulty²,

Ebling³

1999

J. Comp. Neurol.

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In altricial rodents, maternal influences entrain the developing circadian system in the perinatal period before the capacity to respond directly to photic cues develops. The aim of these studies was to investigate the potential role of dopamine in this process in the Siberian hamster. An initial study investigated the ontogeny of retinal innervation of the suprachiasmatic nuclei (SCN) by using cholera toxin B subunit as a tracer. This revealed that retinal fibres first innervate the SCN on postnatal day 3 (PD3), and ingrowth of fibres is extensive by PD6. In situ hybridisation studies revealed the presence of D1-dopamine receptor (D1-R) mRNA in the SCN on PD2, and levels of expression were similar in PD6 pups and adult hamsters. Immunocytochemical staining for tyrosine hydroxylase revealed abundant catecholaminergic fibres within the ventromedial zone of the SCN from the day of birth through PD20; however, in contrast, few fibres were present in adult SCN. Dopamine-beta-hydroxylase-immunoreactive fibres were absent from the neonatal and adult SCN, suggesting that the fibres in the SCN are dopaminergic. The function of this dopaminergic system was investigated by determining the effects of D1-R agonists on the expression of the immediate-early gene c-fos in the SCN. This was assessed in pups ages PD1- PD5 by in situ hybridisation and immunocytochemical localisation of its protein product. No induction was seen in the SCN, in marked contrast to studies in the developing rat. A final series of studies investigated dopaminergic function by determining whether a D1-agonist could induce phosphorylation of Ca2+/cyclic AMP response element-binding protein (CREB) on Ser133. Hypothalamic slices containing SCN taken from PD1 and PD2 hamsters were treated with D1-R agonists, and levels of phosphorylated CREB were assayed by Western blots. Phosphorylation of CREB was stimulated by D1-R agonists in both Syrian and Siberian hamster hypothalamus, but the response was far greater in Syrian hamster tissue (+138%+/-28%) than in Siberian hamster tissue (+43%+/-11%). Although the anatomical studies demonstrate the existence of a dopaminergic system in the SCN of the early postnatal Siberian hamster, the unresponsiveness of c-fos expression and the relative lack of phosphorylation of CREB after D1-R activation suggests a diminished role for dopamine in the regulation of circadian events during the postnatal period in this species.

show abstract

D1 receptors mediate dopamine action in the fetal suprachiasmatic nuclei: studies of mice with targeted deletion of the D1 dopamine receptor gene

Cited by 23 publications

References 21 publications

Anatomical and functional characterisation of a dopaminergic system in the suprachiasmatic nucleus of the neonatal siberian hamster

Anatomical and functional characterisation of a dopaminergic system in the suprachiasmatic nucleus of the neonatal siberian hamster

Circadian modulation of dopamine receptor responsiveness in Drosophila melanogaster

Anatomical and functional characterisation of a dopaminergic system in the suprachiasmatic nucleus of the neonatal siberian hamster

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