Effects of Neonatal Exposure to Methamphetamine: Catecholamine Levels in Brain Areas of the Developing Rat

Abstract

Neonatal exposure to moderate doses of methamphetamine during the first month of life in the rat affects tyrosine hydroxylase gene expression in the substantia nigra and nigrostriatal tyrosine hydroxylase activity. The main goal of this work was to evaluate the ontogeny of the neurochemical effects of repeated exposure to moderate doses of methamphetamine during the first month of life in the rat. Norepinephrine, dopamine, and dihydroxyphenylacetic acid levels were measured in target areas of methamphetamine: the substantia nigra, ventral tegmental area, caudate-putamen, nucleus accumbens, and medial prefrontal cortex. On postnatal day 1 (PND1), Wistar rat litters, culled to eight pups, sex balanced, were randomly attributed to either methamphetamine or control groups. Methamphetamine groups were administered 10 mg of (+/-)-methamphetamine/kg body weight/day, subcutaneously, from PND1 until the day prior to sacrifice; control groups received isovolumetric saline. Groups were sacrificed on PND7, PND14, and PND30. Neonatal methamphetamine exposure increased norepinephrine levels in the substantia nigra of PND30 rats; on PND14, this variation was evident only in male pups. In the substantia nigra, the dihydroxyphenylacetic/dopamine ratio was also affected in PND30 males. In the ventral tegmental area, catecholamine levels were not affected by methamphetamine. Norepinephrine levels were also increased in the caudate-putamen of PND7 male and PND14 female methamphetamine-exposed pups and in the nucleus accumbens of PND14 female and PND30 male and female pups. Catecholamine levels in the medial prefrontal cortex were not affected by neonatal methamphetamine administration.