Public Release: 

Differences in response to amphetamines found between males and females pre-puberty

American Physiological Society

While some Internet sites advise parents that stimulants have the same effect on children as adults, new research on mice indicates this is not the case. Researchers conclude that further differentiation must be made based on gender.

PITTSBURGH, Pa. -- Amphetamine-like drugs are used to treat attention-deficit-hyperactivity disorder (ADHD). These stimulants help people with ADHD learn. They also improve the ability to concentrate, make one less easily distracted, make one less impulsive, and improve one's memory. Children with ADHD are provided drugs like Ritalin upon the recommendation of a physician. Yet, there is little in the research that suggests male and female children may exhibit biological differences in the responses to these stimulants.

Newly released research findings from experiments with mice have established a maturational response to drugs between the known postnatal (up to seven-10 days in rats and mice) and pubertal (around five-six weeks in rats and mice) stages. The findings reveal that differences between males and females in response to drugs begins at an earlier stage than previously believed. During the period after birth, female mice displayed a higher sensitivity to amphetamine well before the onset of puberty, but also well after the early postnatal determination of hormone regulation.

These findings offer a new understanding of male/female differences in brain function and the response to stimuli.

The previous literature focused on two general stages of maturation: (1) The early postnatal "critical period" when sex differences in later hormonal regulation are established (for comparison, mice are born at a stage of brain maturation roughly comparable with a seven-month human fetus) and (2) The time of puberty when sex differences in structure, function, and behavior are manifested.

The authors of the current study, "Differential Sex Effects on Exploratory Behavior in Young Mice Following Selective Monomine Depletion" are Cecile Goodrich Ph.D. (now at Drexel University) and Valerie Robinson. Their findings are being presented at Genomes and Hormones: An Integrative Approach to Gender Differences in Physiology, an American Physiological Society (APS) conference being held October 17-20, 2001, at the Westin Convention Center, Pittsburgh, Pa.

Methodology
To conduct the study, the investigators depleted brain transmitters from the brains of lab mice -- either serotonin (a vascoconstrictor) or catecholamines, (Pyrocatechols with an alkylamine side chain definition) both of which are major elements in response to stress. Behavior was observed at six ages (14, 15, 17, 19, 21, or 28 days). The mice littermates received either p-chlorophenylalanine (pCPA) to deplete the seratonin or a saline solution. Other litters received either a-methyl-p-tyrosine (AMPT) to deplete the catecholarmines or olive oil (for the control group).

Results
Locomotion was observed 24 hours after administration. Locomotion and auditory startle responses were assessed. Analysis revealed that:

  • The female mice treated with pCPA showed significant increases at 19 and 21 days in locomotive ability; males displayed no changes.

  • PCPA females displayed significant increases in startle behavior at 14 days; males had no significant changes.

  • Female mice treated with AMPT had significant decreases in locomotion at 21 and 28 days; male mice decreased their activity at 21 and 28 days. Females in this group displayed significant decreases in startle behavior at 15, 19 and 21 days, whereas males showed no changes from the control group.

Conclusions
The two transmitter systems (serotonin and catecholamines) are known to have different patterns of maturation. This new information on gender differences suggests that additional research may be required to determine the effects of administering stimulants to young boys and girls prior to puberty.

Certain Internet websites advise parents that stimulants have the same effect on children as adults. That is not the case; now further differentiation must be made in considering gender. These animal tests could be an important first step in offering responsible guidance.

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The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

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Contact: Donna Krupa:
703.527.7357
Cell: 703.967.2751 or
djkrupa1@aol.com

Or at The APS Newsroom @
The Westin Convention Center
Pittsburgh, PA
October 17-20, 2001
Tel: 412.281.3700 (The Crawford Room)

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