Ontogeny of the dopamine and serotonin transporters in the rat brain: an autoradiographic study

Galineau, Laurent; Kodas, Ercem; Guilloteau, Denis; Vilar, Marie-Paule; Chalon, Sylvie

doi:10.1016/j.neulet.2004.04.007

Cited by 53 publications

(47 citation statements)

References 25 publications

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“…In contrast, densities of the dopamine transporter were near adult levels in the caudate-putamen and nucleus accumbens at P35 in concordance with previous reports (Galineau et al, 2004). Also in agreement with previous studies of postnatal ontogeny of dopamine receptors (Noisin and Thomas, 1988;Leslie et al, 1991;Rao et al, 1991), the densities of D 1 -like dopamine receptors at P35 were not different from P70 levels in the caudate-putamen and nucleus accumbens; however, the density of D 1 -like receptors in the nucleus accumbens was lower at P70 than at P42 (P Ͻ 0.05) and was accompanied by a small, but significant, increase in affinity.…”

Section: Serum and Brain Methylphenidate Concentrationssupporting

confidence: 92%

Differences in Methylphenidate Dose Response between Periadolescent and Adult Rats in the Familiar Arena-Novel Alcove Task

Levant

Zarcone²,

Davis³

et al. 2010

J Pharmacol Exp Ther

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Methylphenidate is a psychostimulant widely used in the treatment of attention deficit hyperactivity disorder. In this study, the effects of two nonstereotypy-inducing doses of methylphenidate (2.5 and 5.0 mg/kg s.c.) were examined in periadolescent [postnatal days (P) 35 and 42] and young adult (P70), male Long-Evans rats using a three-period locomotor activity paradigm that affords inferences about exploration, habituation, and attention to a novel stimulus (an "alcove") in a familiar environment in a single test session. In the first test period, P35 and P42 rats were more active than P70 rats, and methylphenidate increased locomotion in a dose-related manner. The introduction of a novel spatial stimulus in the third test period revealed a significant interaction of dose and age such that P70 rats exhibited dose-related increases in distance traveled, but P35 rats did not. Furthermore, methylphenidate dose-relatedly disrupted the rats' tendency to spend increasing amounts of time in the alcove across the test period at P70 but not at P35. Brain and serum methylphenidate concentrations were significantly lower at P35 than at P70, with intermediate levels at P42. Developmental differences in dopaminergic neurochemistry were also observed, including increased dopamine content in the caudate-putamen, nucleus accumbens, and frontal cortex and decreased densities of D 1 -like receptors in the frontal cortex in P70 than in P42 rats. These results raise the possibility that children and adults may respond differently when treated with this drug, particularly in situations involving response to novelty and that these effects involve developmental differences in pharmacokinetics and dopaminergic neurochemistry.

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Section: Serum and Brain Methylphenidate Concentrationssupporting

confidence: 92%

Differences in Methylphenidate Dose Response between Periadolescent and Adult Rats in the Familiar Arena-Novel Alcove Task

Levant

Zarcone²,

Davis³

et al. 2010

J Pharmacol Exp Ther

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“…The lesser relative effects of amphetamine could be related to the limited stores available for release in early adolescence as dopamine content and release capacity is less in dorsal striatum of adolescents than adults (Kuhn et al, 2010). Serotonin innervation is also immature in the periadolescents (Moll et al, 2000;Galineau et al, 2004), which is significant because the two dopamine releasers used in these studies would have elevated extracellular serotonin levels more than the DAT inhibitors (Kuczenski and Segal, 1997). Increased serotonin levels should attenuate the hyperlocomotion induced by hyperdopaminergia (Gainetdinov et al, 1999), an effect that should be greater in the adults.…”

Section: Discussionmentioning

confidence: 99%

Dopamine Uptake Inhibitors but Not Dopamine Releasers Induce Greater Increases in Motor Behavior and Extracellular Dopamine in Adolescent Rats Than in Adult Male Rats

Walker

Morris²,

Arrant³

et al. 2010

J Pharmacol Exp Ther

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Most life-long drug addiction begins during adolescence. Important structural and functional changes in brain occur during adolescence and developmental differences in forebrain dopamine systems could mediate a biologic vulnerability to drug addiction during adolescence. Studies investigating age differences in psychostimulant responses have yielded mixed results, possibly because of different mechanisms for increasing extracellular dopamine. Recent research from our laboratory suggests that adolescent dopamine systems may be most affected by selective dopamine uptake inhibitors. We investigated age-related behavioral responses to acute administration of several dopamine uptake inhibitors [methylphenidate, 1-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-4-(3-phenylpropyl)piperazine (GBR12909), and nomifensine] and releasing agents [amphetamine and methylenedioxymethamphetamine (MDMA)] in adolescent and adult male rats. Methylphenidate and amphetamine effects on stimulated dopamine efflux were determined using fast-scan cyclic voltammetry in vivo. Dopamine uptake inhibitors but not dopamine releasing agents induced more locomotion and/or stereotypy in adolescent relative to adult rats. MDMA effects were greater in adults at early time points after dosing. Methylphenidate but not amphetamine induced much greater dopamine efflux in periadolescent relative to adult rats. Periadolescent male rats are particularly sensitive to psychostimulants that are DAT inhibitors but are not internalized and do not release dopamine. Immaturity of DAT and/or DAT associated signaling systems in adolescence specifically enhances behavioral and dopaminergic responses in adolescence.

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“…We compared the DA efflux with data from prior autoradiographic analysis of the maturation of DAT binding [Coulter et al, 1996;Galineau et al, 2004] ( fig. 5 b).…”

Section: Rcbv Response To Da Ligandsmentioning

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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Ontogeny of the dopamine and serotonin transporters in the rat brain: an autoradiographic study

Cited by 53 publications

References 25 publications

Differences in Methylphenidate Dose Response between Periadolescent and Adult Rats in the Familiar Arena-Novel Alcove Task

Differences in Methylphenidate Dose Response between Periadolescent and Adult Rats in the Familiar Arena-Novel Alcove Task

Dopamine Uptake Inhibitors but Not Dopamine Releasers Induce Greater Increases in Motor Behavior and Extracellular Dopamine in Adolescent Rats Than in Adult Male Rats

Pharmacologic Neuroimaging of the Ontogeny of Dopamine Receptor Function

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