Effects of 2,4-dichlorophenoxyacetic acid exposure on dopamine D2-like receptors in rat brain.
2,4-Dichlorophenoxyacetic acid (2,4-D), a worldwide-used herbicide, has been associated with a range of adverse health effects on humans and different animal species. Although the mechanism of 2,4-D neurotoxicity remains unknown, we had previously reported changes in various neurotransmitter systems, such as serotonin (5-HT) and dopamine (DA), which were proposed to mediate some of the behavioral effects in rats. In the present work, we examined the impact of 2,4-D exposure on the ontogeny of dopaminergic D2-type receptors in prefrontal cortex (PFc), striatum (CPu), hippocampus (H) and cerebellum (Cer). Pregnant rats were orally exposed to 70 mg/kg/day of 2,4-D from gestation day (GD) 16 to postpartum day 23. After weaning, the pups were assigned to one of the two subgroups: T1 [fed with untreated diet until postnatal day, (PD) 90] and T2 [maintained with 2,4-D diet until PD 90]. Five to eight pups per age and sex were sacrificed at 6, 15, 30, 45 or 90 days of age for membrane receptor binding assays employing [3H]nemonapride. Subchronic 2,4-D exposure (T2 group) increased DA D2-type receptor around 40% in CPu. In addition, DA D2-type receptor levels also increased in PFc (15 and 30 days) and Cer (30 and 90 days). Sex-dependent differences in D2 receptors were observed with T2 female rats being more affected than T2 male rats. When the herbicide treatment was interrupted after weaning (T1 group), DA D2-type receptor density was apparently recovered and stabilized to control level. These findings suggest a reversible vulnerability of D2-type receptors to 2,4-D exposure. Regional increases of D2-type receptor density may explain certain behaviors reported early by us, such as catalepsy and right-turning preference in rats exposed to 2,4-D.
Bortolozzi
Analía A
AA
Laboratorio de Toxicología Experimental, Faculdad de Ciencias Bioquímicas y Farmacéuticas, UNR, Suipacha 531, Rosario Province, Santa Fe 2.000, Argentina.
Evangelista De Duffard
Ana María
AM
Duffard
Ricardo O
RO
Antonelli
Marta C
MC
D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012737:Sex Factors
D006540:Herbicides; D017448:Receptors, Dopamine D2; D015084:2,4-Dichlorophenoxyacetic Acid