The effects of prenatal exposure to cocaine on the dopaminergic cells in the rat retina. An immunocytochemical and neurochemical study.
There is a growing consensus that the development of the eye is affected by prenatal exposure to cocaine. Considering that the retina is affected by prenatal cocaine exposure, that this drug affects the dopaminergic systems, that the dopaminergic cells in the retina show a well-defined pattern of development and that they can be specifically stained in wholemounts by the antibody anti-tyrosine hydroxylase (TH), this study was undertaken to evaluate the effects of in utero cocaine exposure on the dopaminergic cells of the rat retina. Pregnant Wistar rats were given 60 mg (kg body weight)-1 day-1 of cocaine hydrochloride, subcutaneously, from gestational days 8 to 22. Control groups of pregnant rats were pair-fed. At PND14, 30 and 90, male offspring from different litters were perfused with fixative and the retinas processed as wholemounts and immunostained with the antibody anti-TH. Rats from other groups were decapitated at the same post-natal ages, the retinas dissected and processed by neurochemical techniques to measure the concentrations of dopamine, its metabolites and the turnover of dopamine. There was a significant increase of the retina surface area between PND14-30 in the control group, which was not found in the cocaine group. The density of the immunostained small TH cells was lower in the cocaine groups. No drug-effects were detected in the density of the large TH cells. The densities of the total large and small cells in the superior, inferior and nasal hemiretinas were similar to those found in the whole retinas; however, in the temporal hemiretinas of the cocaine groups, the density of the large TH cells was higher and of the small TH cells was lower than in controls, resulting in an absence of effects on the total density of TH-cells in this hemiretina. A transient increase in the level of dopamine metabolite (DOPAC) and of the turnover of dopamine at PND14 was detected in the cocaine groups. All quantitative parameters reached normal values, in all groups, at PND90. These results show that, during the critical periods in which catecholamines can influence the development of neurons, cocaine transiently affects the pattern of dopaminergic neurons in the retina. This may have functional importance due to the role of this neurotransmitter as a regulatory and/or trophic factor in developing neuronal circuitries.
Silva-Araújo
A
A
Institute for Molecular and Cellular Biology, University of Porto, Portugal.
Silva
M C
MC
Simon
A
A
Nguyen-Legros
J
J
Ali
S F
SF
Tavares
M A
MA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005260:Female; D006719:Homovanillic Acid / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects* / Q000254:growth & development; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine; D004298:Dopamine; D006719:Homovanillic Acid