Effects of postnatal exposure to methamphetamine on the development of the rat retina.

ABSTRACT

Since the development of different cell types in the retina occurs at different rates, it is possible that exposure to an exogenous substance may produce effects during one time period, but not during another. This study aims to analyze the effects of methamphetamine (METH) in the growth pattern of an experimental model as well as neurochemical and immunohistochemical parameters of the dopaminergic system of the rat retina. The three development stages chosen in this study are key markers in rat eye development. Rats were given 15 mg/kg body weight per day of METH as subcutaneous injections in 0.9% saline (3 mL/kg weight/day) from the day after birth PND 1 to PND 6, PND 13, and PND 29. Each daily dose was split into two. The control group was injected subcutaneously with saline. Both the schedule and volume for injecting saline in the control group were the same as for the METH-treated group. There were no significant differences in the total number of offspring per litter among treatment groups. All offspring had similar body weight at birth. Analysis of body weight on PND 1, showed that animals treated with METH had similar body weights to control-treated animals and females had smaller weights than males. For growth evolution, only litters with a sex ratio of four males and four females were used. Animals treated with METH had smaller body weights than the control-treated animals for all ages studied (PND 7, 14, and 30). Within the control group at PND 30, a significant difference was found in the body weight of females, which was lower when compared with males. For the postnatal model, 7 deaths occurred for the METH-exposed group. No deaths occurred in the control group in a total of 16 saline-injected litters comprising 186 pups. Although the levels of dopamine (DA) was within normal values for the postnatally exposed METH group when compared with its respective control group at PND 7 and 30, at PND 14 this was not the case in this experimental group, the level of DA was lower than in the control group for both females and males. Support for this result was not evident from the TH immunoreactivity studies, probably because the methodology lacks the sensitivity to distinguish any mild effects, such as that observed in the postnatal model at PND 14. The level of the DA metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) remained unaffected at all ages studied, for both females and males. The results obtained in this study support the view that, during the critical periods in which the catecholamines can influence the development of neurones, METH transiently affects the pattern of the dopaminergic system in the developing retina.