Effect of amineptine on regional extracellular concentrations of dopamine and noradrenaline in the rat brain.
The effect of amineptine (1.25-20 mg/kg i.p.), an antidepressant inhibiting dopamine uptake, on extracellular concentrations of dopamine was studied in the rat striatum and nucleus accumbens by using the microdialysis technique and two Ca++ concentrations (1.26 and 3.4 mM) in the perfusion medium. In one experiment the effect of amineptine was studied on extracellular concentrations of dopamine and noradrenaline in the frontal cortex perfused with a medium containing 1.26 mM Ca++. Basal extracellular concentrations of dopamine in the striatum and nucleus accumbens were significantly higher at 3.4 mM Ca++. At 5 to 20 mg/kg, amineptine dose-dependently increased extracellular dopamine in the striatum and nucleus accumbens. No differences were found in the effect of amineptine in the two brain regions at the two calcium concentrations. When extracellular dopamine was expressed as a percentage of basal values, amineptine (20 mg/kg) caused greater increases in rats perfused with 1.26 mM Ca++ than in rats perfused with 3.4 mM Ca++ in both brain regions. A similar effect was found when 10 microM amineptine was infused through the dialysis fiber. The effect of 10 mg/kg i.p. of amineptine on dopamine output in the two brain regions was prevented by infusing 1 microM tetrodotoxin in the dialysis fiber. In the frontal cortex, 10 and 20 mg/kg of amineptine significantly raised dopamine and noradrenaline concentrations, whereas 5 mg/kg only increased noradrenaline output significantly. At 10 mg/kg i.p., amineptine also increased extracellular noradrenaline in the dorsal hippocampus. Amineptine had no consistent effects on the concentrations of dihydroxyphenylacetic acid and homovanillic acid in the various brain regions.(ABSTRACT TRUNCATED AT 250 WORDS)
Invernizzi
R
R
Istituto di Ricerche Farmacologiche, Mario Negri, Milano, Italy.
Pozzi
L
L
Vallebuona
F
F
Bonini
I
I
Sacchetti
G
G
Samanin
R
R
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D004298:Dopamine / Q000032:analysis*; D006719:Homovanillic Acid / Q000032:analysis; D008297:Male; D009638:Norepinephrine / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D003986:Dibenzocycloheptenes; D015102:3,4-Dihydroxyphenylacetic Acid; C011597:amineptin; D013779:Tetrodotoxin; D002118:Calcium; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid