Age-related differences in MK-801- and amphetamine-induced locomotor and stereotypic activities of rats

Васильев, В. К.; Veskov, R.; Janać, Branka; Rakić, Lj.; Stojiljković, Mirjana

doi:10.1016/s0197-4580(02)00232-4

Cited by 18 publications

(16 citation statements)

References 37 publications

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“…The mean age and range on the day of the experiment was 28 (27)(28)(29)(30) and 68 (60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77) for the PN28 and PN65 groups, respectively. Varying the frequency of electrical stimulation evokes steady-state responses at low frequencies (20 Hz) as uptake and release are balanced, and linear increases at high frequencies (60 Hz) as release overwhelms uptake.…”

Section: Resultsmentioning

confidence: 99%

“…Several groups have reported that animals in the periadolescent period, , are in general hyperactive, but have smaller increases in locomotion and stereotypic behaviors than younger or older cohorts after single treatments with amphetamine [8,34,70] or cocaine [8,41,63]. Others have reported that adolescents are more responsive to cocaine [11,12,35], amphetamine [1] or nicotine [4,16].…”

Section: Introductionmentioning

confidence: 99%

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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: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cocaine increases stimulated dopamine release more in periadolescent than adult rats

Walker

Kuhn

2008

Neurotoxicology and Teratology

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“…Vasilev et al (2003) reported that amphetamine (1.5 mg/kg) induced less locomotion and stereotyped behavior in PN28 to 30 than 90-day-old adult hooded males. Bolanos et al (1998) also found lower locomotor effects of 0.5 and 1.5 mg/kg amphetamine in PN35 rats than in PN80 male rats.…”

Section: Discussionmentioning

confidence: 97%

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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“…administration [61], thereby exactly coinciding with our T1. Increased locomotion has been reported to last up to 90 min after injection, whereas other side effects like ataxia and head weaving have shorter durations, of around 30 min and 60 min, respectively [60][61][62]. It might therefore be that, in T1, increased locomotion was masked by other side effects that are related to distorted perception and lack of coordination.…”

Section: Pharmacological Deficit Modelsmentioning

confidence: 99%

Object recognition testing: Methodological considerations on exploration and discrimination measures

Akkerman

Blokland

Reneerkens

et al. 2012

Behavioural Brain Research

179

123

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Age-related differences in MK-801- and amphetamine-induced locomotor and stereotypic activities of rats

Cited by 18 publications

References 37 publications

Cocaine increases stimulated dopamine release more in periadolescent than adult rats

Cocaine increases stimulated dopamine release more in periadolescent than adult rats

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

Object recognition testing: Methodological considerations on exploration and discrimination measures

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