title: Mouse strain- and age-dependent effects of binge methamphetamine on dopaminergic signaling.
abstract: We have shown that a single "binge" dose of methamphetamine (Meth) in mice has long-lasting effects on open-field behavior dependent on mouse strain and age. Here we further investigated the impact of genotype and age on tyrosine hydroxylase (TH) loss and dopamine (DA) metabolism due to a high binge dose of Meth (4 × 5 mg/kg × 2 h × 2 days). Administration of high dose Meth or saline (Sal) to adolescent (PND 40) and adult (PND 80) C57BL/6 (B6), DBA/2 (DBA), and 129S6SvEv/Tac (129) mice was followed by a 1mg/kg Meth or Sal (control) challenge 40 days later. Striatal and prefrontal cortex tissues were collected 1h following the challenge. Meth-pretreated adolescent B6 and DBA mice exhibited losses in striatal DA concentrations; DBA adolescents also showed losses in striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and increased DA turnover. Pre-exposed B6 and 129 adults demonstrated significant decreases in striatal DA, DOPAC, and increased DA turnover; DBA adults showed significant losses in striatal DA and increased DA turnover. 129 and DBA adults exhibited increases and decreases, respectively, in prefrontal cortex DA. Adult pretreated B6 mice produced significant losses in striatal TH. The results again show age and genotype dependent differences in Meth-induced DA alterations.
authors.affiliation: University of Colorado Anschutz Medical Campus, Department of Pharmaceutical Sciences, Mail Stop C238, Aurora, CO 80045, USA.
authors.forename: Renee L
authors.initials: RL
authors.lastname: Good
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Liang
authors.forename: Manisha
authors.initials: M
authors.lastname: Patel
authors.forename: Richard A
authors.initials: RA
authors.lastname: Radcliffe
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D019969:Amphetamine-Related Disorders / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000008:administration & dosage*; D015536:Down-Regulation; D005838:Genotype; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010641:Phenotype; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013045:Species Specificity; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine