Selective decreases in amphetamine self-administration and regulation of dopamine transporter function in diabetic rats

Ruggero Galici, Aurelio Galli, David J. Jones, Teresa A. Sanchez, Christine Saunders, Alan Frazer, Georgianna G. Gould, Richard Z. Lin, Charles P. France

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The dopamine transporter (DAT) regulates extracellular dopamine DA levels and is an important site of action for amphetamine and cocaine. Amphetamine and cocaine increase extracellular levels of DA by acting on the DAT; thus, variations in DAT binding sites or activity might influence the action of some drugs of abuse. It was hypothesized that streptozotocin-induced diabetes decreases amphetamine self-administration and that this behavioral change is accompanied by changes in DAT function. Separate groups of male rats responded to receive either amphetamine (0.03 mg/kg/infusion), cocaine (0.25 mg/kg/infusion), or food before and for 7 days after receiving streptozotocin. Rats were sacrificed and [3H]DA uptake and [3H]WIN 35,428 binding were measured in the striatum. In a second study, rats could self-administer one of several different doses of amphetamine (0.01-0.178 mg/kg/infusion) before and after receiving streptozotocin. In streptozotocin-treated rats, a marked decrease in staining for insulin in pancreatic sections was paralleled by a more than doubling in blood glucose levels. Streptozotocin significantly decreased the number of amphetamine infusions without changing the number of cocaine infusions or food pellets received. Streptozotocin increased DA uptake (Vmax) 1.6- or 2.4-fold in rats that responded for food or amphetamine and increased 3-fold the Km for DA only in rats that responded for food; however, [3H]WIN 35,428 binding was not changed in any rat. In the second study, streptozotocin only decreased amphetamine self-administration thereby supporting the view that streptozotocin does not simply decrease the potency of amphetamine. These results demonstrate a selective decrease in amphetamine self-administration in diabetic rats that was associated with increased DAT function in the striatum. Collectively, these studies suggest that insulin pathways in the brain may play an important role in regulating DAT activity and amphetamine action.

Original languageEnglish (US)
Pages (from-to)132-140
Number of pages9
JournalNeuroendocrinology
Volume77
Issue number2
DOIs
StatePublished - 2003

Keywords

  • Amphetamine
  • Catecholamines
  • Cocaine
  • Diabetes
  • Dopamine transporter
  • Insulin
  • Streptozotocin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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