Lead intoxication during intrauterine life and lactation but not during adulthood reduces nucleus accumbens dopamine release as studied by brain microdialysis.
Environmentally relevant levels of lead (Pb) have been demonstrated to have a neurotoxic action, especially on children. In this study, Long-Evans rats were continuously exposed to Pb acetate in drinking water from early gestational days (2-6) or from 28 days of age. At the 13th week of age, the functional activity of the nucleus accumbens (NAC) dopaminergic system was studied by means of transversal microdialysis. Neither Pb treatment regimen modified dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) extracellular concentrations, with respect to control rats. However, neuronal depolarisation, induced by perfusion with 60 mM KCl, increased extracellular DA levels to a significantly minor degree in rats exposed to Pb during the intrauterine life, with respect to both control and adult Pb treated rats. The in utero treated rats also responded with a lower DA release to amphetamine (1 mg/kg ip) administration. On the other hand, no difference in NAC DA level was found amongst treatment groups in response to different concentrations of the D(2)-D(3) dopaminergic agonist quinpirole, locally administered by means of inverse dialysis. These data indicate a preferential impairment of NAC DA synthesis and/or release in rats exposed to Pb acetate during their intrauterine life.
Devoto
P
P
'B.B. Brodie' Department of Neuroscience, Center for Neuropharmacology, C.N.R., University of Cagliari, via Porcell, 4, 09124-I, Cagliari, Italy.
Flore
G
G
Ibba
A
A
Fratta
W
W
Pani
L
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D005260:Female; D007774:Lactation / Q000378:metabolism; D007854:Lead / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans
D015102:3,4-Dihydroxyphenylacetic Acid; D007854:Lead; D004298:Dopamine