title: Glia mechanisms in mood regulation: a novel model of mood disorders.
abstract: BACKGROUND
  Recent evidence in clinical and preclinical studies has implicated glutamate neurotransmissions in pathophysiology of mood disorders. The regulation of amino acid neurotransmission, i.e., glutamate and gamma-aminobutyric acid (GABA) involves coordinated mechanisms of uptake and transport within a tripartite synaptic system that includes neurons and glia. Newly appreciated role of the glia, more specifically astrocytes on neuronal functions combined with reported postmortem abnormalities of glia in patients with mood disorders further supports the role of glia in mood disorders.
  
  
  METHODS
  This report presents some of our preliminary results utilizing glia-selective toxins and other pharmacological tools to suppress glial function within the limbic system to study the resulting behavioral abnormalities, and thus, elucidate glial involvement in the development of mood disorders.
  
  
  CONCLUSIONS
  We demonstrate that chronic blockade of glutamate uptake by a glial/neuronal transporter antagonist L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) within the amygdala, a key area implicated in mood regulation, results in dose-dependent reduction in social exploratory behavior and disrupts circadian activity patterns consistent with symptoms of mood disorders. Similarly, the selective astrocytic glutamate transporter type 1 (GLT-1) blocker dihydrokainic acid (DHK) injected into the amygdala also results in reduced social interaction that is blocked by selective glutamate N-methyl-D-aspartate (NMDA) type receptor antagonist AP5. The results are discussed in the context of glial and glutamate mechanisms in mood disorders and potential therapeutic avenues to address these mechanisms.
authors.affiliation: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Younglim
authors.initials: Y
authors.lastname: Lee
authors.forename: Denise
authors.initials: D
authors.lastname: Gaskins
authors.forename: Amit
authors.initials: A
authors.lastname: Anand
authors.forename: Anantha
authors.initials: A
authors.lastname: Shekhar
mesh_terms: D000339:Affect / Q000187:drug effects; D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D027342:Excitatory Amino Acid Transporter 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005106:Exploratory Behavior / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D019964:Mood Disorders / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012919:Social Behavior
chemical_list: D027322:Amino Acid Transport System X-AG; D003998:Dicarboxylic Acids; D027342:Excitatory Amino Acid Transporter 2; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C020889:dihydrokainic acid; C083486:pyrrolidine-2,4-dicarboxylic acid; D007608:Kainic Acid