Differential effects of acute and short-term lithium administration on dialysate glutamate and GABA levels in the frontal cortex of the conscious rat

In the present study, we employed in vivo microdialysis in the frontal cort ex of the awake rat to investigate the effects of acute and short-term (twi ce daily, 3 days) lithium chloride administration (1, 2, and 4 meq/kg, s.c. ) on local dialysate glutamate and GABA levels. Acute lithium (1 meq/kg) fa iled to influence cortical glutamate levels while the higher (2 and 4 meq/k g) doses increased (+38 +/- 6% ofbasal levels) and reduced (-27 +/- 4%) cor tical glutamate levels, respectively. Cortical GABA levels were affected by acute lithium only at the highest 4 meq/kg dose (+62 +/- 6%). Furthermore, these effects were prevented by tetrodotoxin (1 muM) and low-calcium (0.2 mM) medium perfusion. Following short-term administration, lithium increase d (+58 +/- 4%) cortical dialysate glutamate levels at the 1 meq/kg dose, wa s ineffective at 2 meq/kg, while the effect of the 4 meq/kg dose was simila r to that observed after acute administration. Interestingly, intracortical perfusion with the GABA(B) receptor antagonist CGP 35348 (100 muM) reverse d the acute lithium (4 meq/kg)-induced decrease in glutamate levels. Taken together, these findings indicate a differential dose and duration dependen t effect of lithium on cortical dialysate glutamate levels involving both a direct enhancement and an indirect inhibition that is mediated via an acti vation of local GABA(B) receptor. These findings may be relevant for the th erapeutic effects of the drug. (C) 2000 Wiley-Liss, Inc.