Differences in extracellular glutamate levels in striatum of rats with high and low exploratory activity.

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.

Conclusion: These results suggest that inter-individual differences in exploratory behaviour may be related to striatal glutamatergic neurotransmission.