Neonatal methamphetamine in the rat: evidence for gender-specific differences upon tyrosine hydroxylase enzyme in the dopaminergic nigrostriatal system.

Methamphetamine (Meth) neurotoxicity upon the mesencephalic dopaminergic systems was demonstrated in the adult, both in humans and in experimental models. In the rat, the development and maturation of the dopaminergic systems is accomplished during the first month of postnatal life, a period of particular vulnerability to environmental influences. In this study, the effect of Meth exposure during the first month of life was assessed in the nigrostriatal dopaminergic system of the rat. For this purpose, Wistar rat litters were culled to 8 pups, retaining preferentially 4 males and 4 females, which, in the day following birth (postnatal day 1, PND1), were randomly attributed to either the Meth or control group. Meth-groups were administered 10 mg of (+)-methamphetamine hydrochloride/kg body weight/day, subcutaneously, twice daily, from PND1 until PND29; control groups received isovolumetric doses of saline. Animals were sacrificed at PND30. Males exposed to Meth during the first month of life had increased tyrosine hydroxylase (TH) activity both in the caudate-putamen and substantia nigra. Males also had increased nigral TH mRNA levels, as assessed by in situ hybridization. These effects did not exist in females. These results support the evidence that Meth exposure during the first month of life in the rat has a gender-specific stimulatory effect upon the maturation of TH, the key enzyme for dopamine biosynthesis in the nigrostriatal dopaminergic system.

Developmental exposure to methamphetamine: a neonatal model in the rat.

Taking into account that methamphetamine (MA) is a popular recreational drug among young adult women, i.e., in gestational age, the present model aims to assess the effects of its exposure during development. In this experimental model, MA effects are assessed in the rat during the first month of life, regarding both general growth parameters, and gross morphological effects in the retina as part of the evaluation of sensory systems. Experimental animals were obtained from 60-day-old nulliparous females. Litters were culled to 8 pups (4 males and 4 females, whenever possible), individually marked and weighed every two days. Experimental groups received 10 mg (+)methamphetamine hydrochloride kg body weight/day, subcutaneously, twice daily, from postnatal day (PND) 1 to the day before sacrifice; control groups received isovolumetric doses of saline, in the same protocol. Pups were weaned on PND 21. Groups were sacrificed on PND 5, 7 and 30. Animals exposed to MA presented increased percentage of retinal hemorrhages (18, 7 and 11% on PND 5, 7 and 30, respectively) compound to control groups (2% on PND 7, 0% on PND 5 and 30). On PND 30, the mean body weight of males exposed to MA was 75% of the mean weight of male controls, whereas for females, mean body weights were 70% of those of female controls. These findings support the view that developmental parameters in the rat are deleteriously affected by early exposure to MA.

Developmental Exposure to Methamphetamine: A Neonatal Model in the Rata.

Taking into account that methamphetamine (MA) is a popular recreational drug among young adult women, i.e., in gestational age, the present model aims to assess the effects of its exposure during development. In this experimental model, MA effects are assessed in the rat during the first month of life, regarding both general growth parameters, and gross morphological effects in the retina as part of the evaluation of sensory systems. Experimental animals were obtained from 60-day-old nulliparous females. Litters were culled to 8 pups (4 males and 4 females, whenever possible), individually marked and weighed every two days. Experimental groups received 10 mg (+)methamphetamine hydrochloride kg body weight/day, subcutaneously, twice daily, from postnatal day (PND) 1 to the day before sacrifice; control groups received isovolumetric doses of saline, in the same protocol. Pups were weaned on PND 21. Groups were sacrificed on PND 5, 7 and 30. Animals exposed to MA presented increased percentage of retinal hemorrhages (18, 7 and 11% on PND 5, 7 and 30, respectively) compared to control groups (2% on PND 7, 0% on PND 5 and 30). On PND 30, the mean body weight of males exposed to MA was 75% of the mean weight of male controls, whereas for females, mean body weights were 70% of those of female controls. These findings support the view that developmental parameters in the rat are deleteriously affected by early exposure to MA.