Developmental Regulation of the Dopamine D1 Receptor in Human Caudate and Putamen

Montague, Deidra M.; Lawler, Cindy P.; Mailman, Richard B.; Gilmore, John H.

doi:10.1016/s0893-133x(99)00062-7

Cited by 58 publications

(34 citation statements)

References 52 publications

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“…Although all of the neurochemical "machinery" for dopaminergic transmission is present soon after birth, a number of indices of dopamine function change markedly during adolescence. Overexpression of dopamine D 1 , D 2 and D 4 receptors and subsequent decreases during adolescence have been reported in several studies [3,47,[65][66][67]. Such pruning has also been shown in postmortem studies of adolescent human brain for receptors and the dopamine transporter [44,57].…”

Section: Introductionmentioning

confidence: 71%

“…In fact, basal extracellular dopamine concentrations measured by microdialysis are reported to be lower than adult values in 33-43 day old rats [2] and in 35-36 day olds [36]. In contrast to lower extracellular dopamine in adolescents, striatal D 1 and D 2 receptor levels are higher in adolescent than adult humans [47,48,58] and rats [65,66]. The combination of more dopamine being released due to DAT inhibition onto more, or more sensitive, receptors could synergistically contribute to the greater behavioral response to cocaine that we reported [11].…”

Section: Discussionmentioning

confidence: 95%

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Cocaine increases stimulated dopamine release more in periadolescent than adult rats

Walker

Kuhn

2008

Neurotoxicology and Teratology

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The neural mechanisms responsible for the enhanced adolescent vulnerability for initiating drug abuse are unclear. We investigated whether age differences in dopamine neurotransmission could explain cocaine's enhanced psychomotor effects in the periadolescent rat. Electrical stimulation the medial forebrain bundle of anesthetized post-natal age 28 days (PN28) and PN65 rats elicited dopamine release in caudate nucleus and nucleus accumbens core before and after 15 mg/kg cocaine i.p. Extracellular dopamine concentrations were greater in PN65 than PN28 caudate following 20 and 60Hz stimulations and in the PN65 nucleus accumbens following 60Hz stimulations. Cocaine increased dopamine concentrations elicited by 20 Hz stimulations 3-fold in the adult, but almost 9-fold in periadolescent caudate. Dopamine release rate was lower in the periadolescent caudate although total dopamine clearance was similar to that of adults. The periadolescent caudate achieved adult levels of clearance by compensating for a lower V max with higher uptake affinity. Tighter regulation of extracellular dopamine by the higher uptake/release ratio in periadolescents led to greater increases after cocaine. In nucleus accumbens, dopamine release and V max were lower in periadolescents than adults, but uptake affinity and cocaine effects were similar. Immaturity of dopamine neurotransmission in dorsal striatum may underlie enhanced acute responses to psychostimulants in adolescent rats and suggests a mechanism for the greater vulnerability of adolescent humans to drug addiction.

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Section: Introductionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 95%

Cocaine increases stimulated dopamine release more in periadolescent than adult rats

Walker

Kuhn

2008

Neurotoxicology and Teratology

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“…In young rats, the relative populations of D1R and D2R and the proportion of each receptor at its high affinity state are not clear. Studies using quantitative autoradiography in rodents and primates showed that there was an initial overproduction followed by a declination of the dopamine D1R and D2R during adolescence [Montague et al, 1999;Andersen et al, 2000], although little evidence indicates that these two ontogenic processes are in synchrony. The rCBV decreases to cocaine and MPH challenge suggests that, at young ages, extracellular DA binds more efficiently to D2R than D1R.…”

Section: Discussionmentioning

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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“…These observations are not surprising as the presence or absence of sex hormones is only one factor that could affect behavioral responsiveness to stimulants across adolescence. Forebrain dopamine systems continue to mature and reorganize across adolescence (Haycock et al 2003;Montague et al 1999;Teicher et al 1995;reviewed in Spear 2000). For example, it has been shown that there is an overproduction and regressive pruning of striatal dopamine receptors during adolescence (Teicher et al 1995).…”

Section: : Discussionmentioning

confidence: 99%

Gonadal steroids mediate the opposite changes in cocaine-induced locomotion across adolescence in male and female rats

Parylak

Caster

Walker

et al. 2008

Pharmacology Biochemistry and Behavior

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Evidence from both human studies and animal models indicates that cocaine elicits more behavioral stimulation in females than males. The present study sought to determine whether sex-specific responses to cocaine emerge during adolescence and to determine if gonadal steroid action during puberty affects adult responsiveness to cocaine. We administered cocaine using an escalating dose model in male and female rats at ages postnatal (PN) 28, 42, and 65 days. To assess the effects of pubertal gonadal steroid action, we compared the effects of binge cocaine administration on intact and prepubertally gonadectomized male and female rats in adulthood. Cocaine responses changed in opposite directions in males and females as they progressed through adolescence. At most doses, adolescent males were more responsive than adult males whereas adult females were more responsive than adolescent females. Ambulatory activity was age-dependent in males whereas non-ambulatory activity was age-dependent in females. Prepubertal gonadectomy increased behavioral responsiveness to the highest dose of cocaine in males whereas it decreased behavioral responsiveness to lower doses of cocaine in females. We conclude that sex differences in behavioral responses to cocaine arise during adolescence from a concurrent decrease in male responsiveness and increase in female responsiveness. Our results suggest that gonadal steroids exert lasting and opposing effects on the sensitivity of males and females to psychostimulants during development.

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Developmental Regulation of the Dopamine D1 Receptor in Human Caudate and Putamen

Abstract: Perturbations in the developmental

Cited by 58 publications

References 52 publications

Cocaine increases stimulated dopamine release more in periadolescent than adult rats

Cocaine increases stimulated dopamine release more in periadolescent than adult rats

Pharmacologic Neuroimaging of the Ontogeny of Dopamine Receptor Function

Gonadal steroids mediate the opposite changes in cocaine-induced locomotion across adolescence in male and female rats

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