Asymmetrical development of the monoamine systems in 2,4-dichlorophenoxyacetic acid treated rats.
The purpose of this study was to determine whether the regional brain biogenic amine levels in adult rats were altered by pre- and post-natal exposure to 2,4-dichlorophenoxyacetic acid (2,4-D). Pregnant rats were daily orally exposed to 70 mg/kg per day of 2,4-D from gestation day (GD) 16 to post-partum day (PPD) 23. After weaning, the pups were assigned to one of two subgroups: T1 fed with untreated diet up to post-natal day (PND) 90 and T2 (maintained with 2,4-D diet up to PND 90). In addition, we wanted to know the effect of 2,4-D on lateralization in the monoamine systems of the basal ganglia of these adult rats and whether there was any correlation with the behavioral developmental pattern previously reported by us. In this study the content of noradrenaline (NA) was significantly increased in substantia nigra (SN) while it decreased in cerebellum in male and female rats of T2 group. The decreased dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovallinic acid (HVA) contents in cerebellum, midbrain, ventral tegmental area (VTA) and prefrontal cortex (PFc) showed an alteration in the mesocorticolimbic system. However, an increase of DA in SN and of DOPAC and HVA in nucleus accumbens (NAc) in both sexes and of DA and DOPAC (only in females) in striatum was detected. The contents of serotonin (5-hydroxytryptamine, 5-HT) were significantly increased in both sexes in PFc, striatum (St), midbrain, SN and cerebellum. Variations of any monoamine levels in NAc and VTA were determined. T1 rats were irreversibly altered: a diminution in DA and/or DOPAC levels in PFc, midbrain, VTA and cerebellum was determined. Indolamines of these rats were increased in both sexes in PFc and St. There was also a large increase in 5-HT levels in midbrain of male rats. Although no changes in the dopaminergic system with respect to their control values in any side of these brain structures were observed, DA and DOPAC levels were found to be decreased in the right side with respect to the left side in striata and accumbens nuclei in T2 female rats supporting the behavioral rotation previously registered by us in these rats. In addition, the increased 5-HT content detected in both the right and left striata observed in this study could be the answer to the behaviors observed and to the early alterations in dopamine in basal ganglia by 2,4-D in neonatal exposed rats, mediated by a serotonergic modulation on the dopaminergic system.
Bortolozzi
Analía
A
Experimental Toxicology Laboratory, Biochemical and Pharmaceutical Faculty, UNR, Suipacha 531, 2000 Rosario, Argentina.
Duffard
Ricardo
R
de Duffard
Ana María Evangelista
AM
D015084:2,4-Dichlorophenoxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D005260:Female; D007839:Functional Laterality / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar
D015306:Biogenic Monoamines; D015084:2,4-Dichlorophenoxyacetic Acid