Differential effects of methylphenidate on the growth of neonatal and adolescent rats.

Methylphenidate (MPH), the drug of choice in the treatment of Attention Deficit Disorders with Hyperactivity (ADD/H), has raised concern regarding its suspected potential for reducing body stature in growing patients. In a previous study we demonstrated that neonatal rats treated with MPH (35 mg/kg, SC, twice daily) showed an acute growth impairment followed by a rapid growth-rebound phenomenon. This report confirms our earlier findings in neonatal rats and extends the investigation of the growth suppressing effects of MPH to the periadolescent period of development in rats. Specifically, neonatal groups of male and female rats treated with higher and lower doses of MPH than in the original study confirmed the growth impairment and growth rebound phenomena reported earlier. Unlike neonatal rats, rats treated during the periadolescent period of development failed to show any growth impairment. These data suggest that the growth suppressing effects of MPH are the result of an acute toxicity which is readily reversible on discontinuation of the drug. Further, it is concluded that there is a low probability of long term effects on human body stature when the minimal therapeutic dose is used in clinical practice.

Methylphenidate and growth: demonstration of a growth impairment and a growth-rebound phenomenon.

Methylphenidate (MPH), the drug of choice in the treatment of attention deficit disorder with hyperactivity (ADD/H), has been shown to reduce the body stature of some patients. The present study was undertaken to determine if MPH suppresses growth in rats, and whether the clinical observation of a growth rebound phenomenon could be experimentally demonstrated. Our results demonstrate that neonatal rats treated with MPH show a reduction in femur length and a reduction in thyroid, pituitary, testis, adrenal gland, and brain weights immediately following drug cessation. However, a growth-rebound phenomenon occurs such that there are no differences between treated and control groups within 30 days of the last drug exposure. These data, along with those from the clinical literature, suggest that growth impairment is most likely a result of the acute effects of the drug. Further, these data suggest that when administered at therapeutic doses which avoid significant weight loss in the patient, MPH is not likely to cause growth impairment in children.

The Monosodium L-glutamate (MSG) syndrome in mice develops independently of housing condition.

The sequelae of neuroendocrine, somatic, and behavioral deficits following neonatal MSG treatment have been well-documented, including obesity and decreased locomotor activity. Recently, it was reported that increased body weight and decreased locomotor activity occurred only in group-housed animals. The studies reported here were designed to systematically explore the effects of housing conditions on MSG-treated mice. All aspects of the MSG syndrome were obtained, regardless of the housing condition. We conclude that housing variables play no role in the production of the MSG syndrome in mice. While all MSG-treatment mice had reduced brain weights (cerebrum) regardless of housing condition, MSG-treated mice raised individually had significantly lighter brains than MSG-treated mice raised in groups.

Reproductive dysfunction in male rats following neonatal administration of monosodium L-glutamate.

Monosodium glutamate (MSG) was administered to neonatal rats according to an increasing dose schedule from days 2-11 after birth. Adult MSG-treated male rats showed reproductive deficits along with stunted body lengths and reduced testes weights. These results demonstrate that MSG is capable of producing reproductive deficits in the rat similar to those seen in the mouse. These results are discussed in light of the methodological differences between those studies reporting positive or negative findings on reproductive function in MSG-treated mice and rats.

Somatic, behavioral, and reproductive disturbances in mice following neonatal administration of sodium L-aspartate.

Sodium L-aspartate (ASP) was administered to neonatal mice according to an increasing dose schedule from Days 2--11 after birth. Adult ASP-treated animals showed large increases in body weight over controls along with stunted body length. The ASP group also showed decreases in locomotor and exploratory behavior. Reproductive dysfunction occurred in both female and male ASP-treated animals. Among treated animals, females had fewer pregnancies and smaller litters while males showed reduced fertility. Evidence of multiple endocrine dysfunction in ASP-treated animals was reflected by decreased pituitary, thyroid, ovaries and tested weights, along with delayed onset of puberty in females. These results demonstrate that sodium L-aspartate produces a syndrome similar to that seen following the administration of monosodium L-glutamate.

Monosodium glutamate admlinistration to the newborn reduces reproductive ability in female and male mice.

Monosodium glutamate (MSG) administered during the neonatal period (days 2 to 11) resulted in a sequence of events that were manifested in adulthood. Reproductive dysfunction was seen in both female and male animals. Females treated with MSG had fewer pregnancies and smaller litters, while males treated with MSG showed reduced fertility. The MSG-treated mice showed increased body weight and decreased pituitary, thyroid, ovary, or testis weights.

Effects of monosodium glutamate on somatic development, obesity and activity in the mouse.

Neonatal mice 1 and 5 days of age and older mice 25 days of age were injected with an increasing dose of monosodium glutamate (MSG) for a ten-day period and observed for at least 150 days. Both male and female animals in the 1- and 5-day age group treated with MSG showed large increases in weight over controls along with a shortened body length. The MSG group also showed decreases in locomotor and explatory behavior. The 25-day animals took much longer to show effects or failed to show any effects, indicating that the MSG-induced changes studied are age dependent. Possible methodological considerations accounting for conflicting reports in the MSG literature are discussed in light of the present findings.