title: Differential effects of acute and short-term lithium administration on dialysate glutamate and GABA levels in the frontal cortex of the conscious rat.
abstract: In the present study, we employed in vivo microdialysis in the frontal cortex of the awake rat to investigate the effects of acute and short-term (twice 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) failed to influence cortical glutamate levels while the higher (2 and 4 meq/kg) doses increased (+38 +/- 6% of basal levels) and reduced (-27 +/- 4%) cortical 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 microM) and low-calcium (0.2 mM) medium perfusion. Following short-term administration, lithium increased (+58 +/- 4%) cortical dialysate glutamate levels at the 1 meq/kg dose, was ineffective at 2 meq/kg, while the effect of the 4 meq/kg dose was similar to that observed after acute administration. Interestingly, intracortical perfusion with the GABA(B) receptor antagonist CGP 35348 (100 microM) reversed the acute lithium (4 meq/kg)-induced decrease in glutamate levels. Taken together, these findings indicate a differential dose and duration dependent effect of lithium on cortical dialysate glutamate levels involving both a direct enhancement and an indirect inhibition that is mediated via an activation of local GABA(B) receptor. These findings may be relevant for the therapeutic effects of the drug.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Ferrara, Ferrara, Italy. ant@ifeuniv.unife.it
authors.forename: T
authors.initials: T
authors.lastname: Antonelli
authors.forename: V
authors.initials: V
authors.lastname: Ferioli
authors.forename: G
authors.initials: G
authors.lastname: Lo Gallo
authors.forename: M C
authors.initials: MC
authors.lastname: Tomasini
authors.forename: M
authors.initials: M
authors.lastname: Fernandez
authors.forename: W T
authors.initials: WT
authors.lastname: O'Connor
authors.forename: J C
authors.initials: JC
authors.lastname: Glennon
authors.forename: S
authors.initials: S
authors.lastname: Tanganelli
authors.forename: L
authors.initials: L
authors.lastname: Ferraro
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D018698:Glutamic Acid / Q000187:drug effects* / Q000378:metabolism; D018021:Lithium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018692:Antimanic Agents; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D018021:Lithium Chloride