Ontogenetic differences in the psychopharmacological responses to separate and combined stimulation of D1 and D2 dopamine receptors during the neonatal to weanling age period

Moody, Carole A.; Spear, Linda P.

doi:10.1007/bf02801967

Cited by 64 publications

(58 citation statements)

References 33 publications

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“…As noted in previous studies on rats (Eilam et al, 1992;Meyer and Shults, 1993;Mogenson and Wu, 1991;Moody and Spear, 1992), the DAD1-like agonists tested in the present study either elevated or reduced the locomotion of C57 mice, the particular effect depending upon dose and testing conditions. However, in contrast to the several reports indicating that DAD2-like agonists produce a biphasic action on motor activity of rats (Eilam and Szechtman, 1989;Hartesveldt et al, 1994;, quinpirole produced a monotonic reduction in locomotion of C57 mice.…”

Section: Discussionmentioning

confidence: 58%

“…For example, the partial DAD1 agonist SKF 38393 was reported to reduce the activity of Sprague-Dawley rats at a low dose of 0.01 mg/kg; however, a high dose (10 mg/kg) elevated activity (Meyer and Shults, 1993;Moody and Spear, 1992). A similar biphasic doseresponse effect was reported for the full DAD1 agonist, SKF 82958 (Meyer and Shults, 1993).…”

Section: Introductionmentioning

confidence: 60%

“…Later in the test, while the activity of vehicle-injected mice declined, the activity of SKF 38393-injected mice remained relatively constant, resulting in elevated activity relative to control levels. Furthermore, Moody and Spear (1992) reported that SKF 38393 elevated the activity of Sprague-Dawley rat pups when control activity levels were low. To illustrate the generality of the motor activity increase associated with SKF 38393, several studies indicated that intraaccumbens infusions of SKF 38393 increased locomotor activity of various rat strains (Dreher and Jackson, 1989;Meyer, 1993;, and additional studies indicated that SKF 38393 elevated activity when injected (IP or SC) into either mice (Arnt et al, 1992;Shannon et al, 1991;Zarrindast and Eliassi, 1991) or rats (Bruhwyler et al, 1991;Mazurski and Beninger, 1991;Waddington, 1985, 1987;Molloy et al, 1985;Setler et al, 1978).…”

Section: Discussionmentioning

confidence: 97%

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DAD1- and DAD2-like agonist effects on motor activity of C57 mice: Differences compared to rats

Halberda

Middaugh

Gard

et al. 1997

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Studies on rats indicate that DAD1- and DAD2-like agonists produce a biphasic action on motor activity, with low doses reducing activity below control levels, and higher doses initially reducing, then elevating, activity for a prolonged period. Although some of the reported effects of DAD1- and DAD2-like receptor agonists on motor activity of mice are consistent with their effects on rats, the possibility of species differences is also apparent. In the current study the effects of DAD1- and DAD2-like agonists on motor activity of C57BL/6 (C57) mice were determined to establish species consistencies and differences with respect to their effects on rats. The partial DAD1-like agonist SKF 38393 reduced the activity of C57 mice at low doses and elevated activity above control levels at higher doses, if the mice were thoroughly habituated to the test chamber. The full DAD1 agonist SKF 82958 also increased the activity of C57 mice, and along with the SKF 38393 results indicates a response to DAD1 receptor stimulation similar to that reported for rats. In contrast to the species similarity in response to DAD1 stimulation, the DAD2-like agonist quinpirole produced only a dose-responsive monotonic reduction in the activity of C57 mice, whether the animals were nonhabituated or well-habituated to the testing environment, male or female, young or mid-aged, injected intraperitoneally (i.p.) or subcutaneously (s.c.), and with either low or high doses. This apparent species difference in response to quinpirole might reflect distinguishable functional properties of the DA subreceptor systems.

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Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 97%

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DAD1- and DAD2-like agonist effects on motor activity of C57 mice: Differences compared to rats

Halberda

Middaugh

Gard

et al. 1997

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“…This stimulatory locomotor response to D1R agonists has generally been found to be lower in infant (5-10 d old) rats compared with weanling rats (13,14). The difference has varied depending on the dose and preparation of D1R agonist as well as on whether the animals have been habituated to the cage or not.…”

Section: Discussionmentioning

confidence: 99%

Locomotor Effects of a D1R Agonist Are DARPP-32 Dependent in Adult but not Weanling Mice

et al. 2005

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Evidence suggests that dopamine regulation of motor activity undergoes postnatal maturation. To examine the role of the dopamine 1 receptor (D1R)/dopamine-and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) signaling pathway for this maturation, we studied the effects of a D1R agonist on motor activity in weanling and adult wild-type (WT) mice and mice that lack DARPP-32, a key messenger in the D1R signaling pathway. Locomotor activity was not affected by D1R activation in WT weanling mice but was significantly stimulated in WT adult mice. This stimulation was absent in DARPP-32 (Ϫ/Ϫ) adult mice. In contrast, the inhibitory effects that were observed on rearing activity in WT weanling and adult mice were present in Dopamine plays a central role in the control of motor activity and cognitive functions. Alterations in the dopamine system have been linked to a number of disorders, including attention-deficit/hyperactivity disorder (ADHD), the most common neuropsychiatric disorder in children and young teenagers (1). Numerous studies in children with ADHD have demonstrated that potentiating of the action of dopamine via psychostimulants has a positive effect on hyperactivity (2).The downstream effects of dopamine are mediated via a complex interaction between the two subtypes of dopamine receptors, D1-and D2-like receptors (3). Dopamine-and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) plays an important role in mediating the actions of dopamine and other neurotransmitters that act on dopaminoceptive neurons. DARPP-32 is phosphorylated by activation of D1 receptors (D1R) via the cAMP pathway. DARPP-32 in its activated state is a potent inhibitor of protein phosphatase-1 (PP-1) (4). Several signaling pathways converge on DARPP-32, making it a main modulator of many downstream effects of D1R activation (5). Studies using DARPP-32-deficient mice have indicated that DARPP-32 is involved in mediating effects of many psychostimulant and antipsychotic drugs (6). Recent work in rats from our laboratory has shown that D1R activation can have both inhibitory and stimulatory effects on motor activity (7). However, little is known about the signaling pathways that mediate these effects.Here we have investigated whether D1R-mediated motor inhibitory and stimulatory effects are dependent on the DARPP-32 signaling pathway, as well as on postnatal maturational changes. For this purpose, we investigated the motor responses to the full and selective D1-like receptor agonist (8) SKF-81297 in nonhabituated weanling and adult wild-type (ϩ/ϩ) (WT) and DARPP-32 (Ϫ/Ϫ) mice. The use of a model in which the animals had a high baseline activity (nonhabituated) made it possible to examine not only stimulatory but also inhibitory motor response to D1R activation. METHODSSubjects. Weanling (3 wk old) and adult (12-15 wk old) male WT (ϩ/ϩ) and DARPP-32 (Ϫ/Ϫ) male mice were used. The animals were obtained from the Rockefeller University and were generated from C57BL/6 mice as previously described (6). The WT and DARPP-32 (Ϫ/Ϫ) mice used in...

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“…A few papers showed higher values in animals at around P35-45, which then decrease in adulthood, but the data here are under-powered to conclusively show such an effect. In figure 6 b the mRNA expression levels are shown [Chen and Weiss, 1991;Creese et al, 1992;Guennoun and Bloch, 1992;Moody and Spear, 1992a;Srivastava et al, 1992;Weiss et al, 1992;Schambra et al, 1994;Filloux et al, 1996;Flores et al, 1996;Jung and Bennett, 1996]. The pattern with regards to the D1 and D2 seems quite different at the early ages ( !…”

Section: Meta-analysis Of Literature Datamentioning

confidence: 99%

Pharmacologic Neuroimaging of the Ontogeny of Dopamine Receptor Function

Chen

Choi

et al. 2010

Dev Neurosci

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Characterization of the ontogeny of the cerebral dopaminergic system is crucial for gaining a greater understanding of normal brain development and its alterations in response to drugs of abuse or conditions such as attention-deficit hyperactivity disorder. Pharmacological MRI (phMRI) was used to determine the response to dopamine transporter (DAT) blockers cocaine and methylphenidate (MPH), the dopamine releaser D-amphetamine (AMPH), the selective D1 agonist dihydrexidine, and the D2/D3 agonist quinpirole in young (<30 days old) and adult (>60 days old) rats. In adult rats, cocaine (0.5 mg/kg i.v.) or MPH (2 mg/kg) induced primarily positive cerebral blood volume (rCBV) changes in the dopaminergic circuitry, but negative rCBV changes in the young animals. Microdialysis measurements in the striatum showed that young rats have a smaller increase in extracellular dopamine in response to cocaine than adults. The young rats showed little rCBV response to the selective D1 agonist dihydrexidine in contrast to robust rCBV increases observed in the adults, whereas there was a similar negative rCBV response in the young and adult rats to the D2 agonist quinpirole. We also performed a meta-analysis of literature data on the development of D1 and D2 receptors and the DAT. These data suggest a predominance of D2-like over D1-like function between 20 and 30 days of age. These combined results suggested that the dopamine D1 receptor is functionally inhibited at young age.

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Ontogenetic differences in the psychopharmacological responses to separate and combined stimulation of D1 and D2 dopamine receptors during the neonatal to weanling age period

Cited by 64 publications

References 33 publications

DAD1- and DAD2-like agonist effects on motor activity of C57 mice: Differences compared to rats

DAD1- and DAD2-like agonist effects on motor activity of C57 mice: Differences compared to rats

Locomotor Effects of a D1R Agonist Are DARPP-32 Dependent in Adult but not Weanling Mice

Pharmacologic Neuroimaging of the Ontogeny of Dopamine Receptor Function

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