title: Differences in extracellular glutamate levels in striatum of rats with high and low exploratory activity.
abstract: BACKGROUND
  Major inter-individual differences exist in vulnerability to anxiety and affective disorders, and the underlying neurobiology could help in understanding the predisposition to these disorders and treatment resistance. Recently the glutamatergic system has become a target in the development of novel antidepressants.
  
  
  METHODS
  We compared extracellular glutamate levels in low (LE-) and high exploring (HE-) rats in hippocampus and striatum at baseline and after inhibition of re-uptake by perfusion with l-trans-pyrrolidine-2,4-dicarboxylate (PDC, 4mM). Glutamate levels in microdialysates were measured by HPLC after derivatization.
  
  
  RESULTS
  In the striatum, baseline glutamate levels in young adult LE-rats and HE-rats were not significantly different, but the response to uptake inhibition was: perfusion with PDC increased extracellular glutamate levels in both LE- and HE-rats, but to a significantly lower extent in LE-rats. Although the characteristic levels of exploration of LE- and HE-rats had previously been shown to be stable up to 8 months of age, we identified a subgroup of HE-rats whose exploration levels had drastically dropped by age of 11 months (formerly HE-rats, HEF), and analyzed their data separately. There were no differences in the PDC-evoked striatal glutamate release between the three groups; however, the baseline glutamate levels were higher in the HEF-subgroup compared to the HE- and LE-animals. In the CA1 area of hippocampus, there were no differences in extracellular glutamate levels between the LE- and HE-rats either at baseline or after inhibition of uptake.
  
  
  CONCLUSIONS
  These results suggest that inter-individual differences in exploratory behaviour may be related to striatal glutamatergic neurotransmission.
authors.affiliation: Division of Neuropsychopharmacology, Department of Psychology, Estonian Centre of Behavioural and Health Sciences, University of Tartu, Tartu, Estonia.
authors.forename: Karita
authors.initials: K
authors.lastname: Raudkivi
authors.affiliation: Division of Neuropsychopharmacology, Department of Psychology, Estonian Centre of Behavioural and Health Sciences, University of Tartu, Tartu, Estonia.
authors.forename: Aet
authors.initials: A
authors.lastname: Alttoa
authors.affiliation: Institute of Chemistry, University of Tartu, Tartu, Estonia.
authors.forename: Ivo
authors.initials: I
authors.lastname: Leito
authors.affiliation: Division of Neuropsychopharmacology, Department of Psychology, Estonian Centre of Behavioural and Health Sciences, University of Tartu, Tartu, Estonia. Electronic address: jaanus.harro@ut.ee.
authors.forename: Jaanus
authors.initials: J
authors.lastname: Harro
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D003998:Dicarboxylic Acids / Q000494:pharmacology; D005106:Exploratory Behavior / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003998:Dicarboxylic Acids; D011759:Pyrrolidines; D018698:Glutamic Acid; C083486:pyrrolidine-2,4-dicarboxylic acid
keywords: Anxiety; Depression; Exploratory behaviour; Glutamate; Individual differences