title: Withdrawal from chronic amphetamine reduces dopamine transmission in the rat lateral septum.
abstract: The lateral septum (LS) is a brain nucleus implicated in the addictive process. This study investigated whether withdrawal from chronic amphetamine (AMPH) induces alterations in dopamine (DA) transmission within the LS. Male Sprague-Dawley rats were injected with AMPH (2.5 mg/kg i.p.) or saline during 14 days and thereafter subjected to 24 hr or 14 days of withdrawal. After these withdrawal periods, we measured DA extracellular levels by in vivo microdialysis, DA tissue levels, and tyrosine hydroxylase (TH) and vesicular monoamine transporter-2 (VMAT2) expression in the LS. Our results showed a significant decrease in K(+) -induced release of DA in the LS of AMPH-treated rats, 14 days after withdrawal compared with saline-treated rats. There were no significant differences in DA tissue content and TH expression. Interestingly, there was a decrease of LS VMAT2 expression in AMPH-treated rats, 14 days after withdrawal compared with saline-treated rats. This is the first neurochemical evidence showing that withdrawal from repeated AMPH administration decreases K(+) -induced DA release in the rat LS. Our results suggest that this decrease in DA releasability could be due to a decrease in DA vesicular uptake. The possibility that these neurochemical changes are associated with AMPH abstinence syndrome should be further explored.
authors.affiliation: Millennium Science Nucleus in Stress and Addiction, Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Georgina M
authors.initials: GM
authors.lastname: Renard
authors.forename: Ramón
authors.initials: R
authors.lastname: Sotomayor-Zarate
authors.forename: Elías H
authors.initials: EH
authors.lastname: Blanco
authors.forename: Katia
authors.initials: K
authors.lastname: Gysling
mesh_terms: D000661:Amphetamine / Q000009:adverse effects*; D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000187:drug effects*; D018709:Statistics, Nonparametric; D013375:Substance Withdrawal Syndrome / Q000473:pathology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: abstinence; addiction; dopamine releasability; psychostimulants