Acid metabolites of monoamines in avian brain; effects of probenecid and reserpine

Abstract

1 The concentration of the dopamine (DA) metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the anterior part of the nucleus basalis of pigeon brain was found to be 0.17 ± 0.01 μg/g, which is about one-fifth of the concentration of homovanillic acid (HVA) in this region. In the chicken, the concentration of HVA in the (entire) nucleus basalis was 0.06 ± 0.006 μg/g, lower than in any other species examined, and giving a ratio of DA to HVA of about 50. The concentration of DOPAC in the 8 day old chick was 0.053 ± 0.002 μg/g. 2 Probenecid, 200 mg/kg intramuscularly, doubled the content of DOPAC in the nucleus basalis of the pigeon and increased the concentration of HVA in both the pigeon and the chicken by a factor of 4 to 5. These findings demonstrate the existence, in avian brain, of an active transport mechanism for the removal of acidic substances and explain the low concentrations of the acids found in bird brain. 3 A method is described for the estimation of 5-hydroxytryptamine (5-HT) and 5-hydroxyindolylacetic acid (5-HIAA) in the same tissue sample. Probenecid caused an increase in the 5-HIAA content but produced no change in the 5-HT content of the nucleus basalis of pigeon brain. 4 Reserpine caused a fall in the content of acidic DA metabolites in the nucleus basalis of the pigeon. The effect was more pronounced after raising the concentration of these acids with probenecid. 5 Treatment of pigeons with pargyline (100 mg/kg 17 hr before decapitation) did not significantly increase the DA content of the nucleus basalis, but it prevented to some extent the loss in DA caused by reserpine. 6 Pigeons and chickens were sedated by probenecid. The deepest sedation occurred at about the same time as the greatest increase in the acidic amine metabolites in the brain. 7 Intracisternal injection of HVA in the pigeon and intravenous injection of large amounts of HVA, DOPAC, 5-HIAA or 3,4-dimethoxyphenylacetic acid into newly hatched chicks did not produce any sedation or other effects on behaviour. In contrast, injection of sodium γ-hydroxybutyrate caused paralysis followed by prostration and eye closure. 8 Estimation of the concentration of HVA in the brain of the young chick after intravenous injection of the acid (100 mg/kg) showed that the concentration was of the same order of magnitude as it is in animals given probenecid; this suggests that the sedation which follows probenecid is not related to the accumulation of acidic amine metabolites.