ADHD News

http://www.medicalnewstoday.com/medi...p?newsid=74654

ADHD News


Parents, doctors, and others have wondered whether common treatments for
attention-deficit hyperactivity disorder (ADHD) inadvertently predispose
adolescents to future drug abuse. The answer may depend on the age at which
treatment is started and how long it lasts, say the authors of a new
brain-imaging and behavioral study conducted in animals at the U.S.
Department of Energy's Brookhaven National Laboratory. The results appeared
in the online issue of the journal Pharmacology, Biochemistry and Behavior.

"Our study shows that the brain's reward pathways are definitely influenced
by methylphenidate, one of the stimulant drugs commonly used to treat ADHD,"
said Brookhaven researcher Panayotis (Peter) Thanos, lead author of the
study. "But the brain chemistry changes we observed suggest that the
developmental stage at which treatment begins and the duration of treatment
are important variables that need further study."

In the study, rats were given methylphenidate mixed with distilled water
beginning one month after birth -- early adolescence for rats. Animals
received either 1 or 2 milligrams methylphenidate per kilogram of body
weight, consistent with clinical doses given to children with ADHD. A
control group of rats was handled under identical conditions but given plain
water.

After two months of treatment, and again after eight months, the scientists
performed positron emission tomography (PET) scans to measure the levels of
dopamine D2 receptors, a type of brain receptor important for experiencing
reward and pleasure that has been linked to pleasure and drug abuse. After
the eight-month treatment, animals were also tested for their propensity to
self-administer cocaine.

Rats given the 2mg/kg dose of methylphenidate were significantly less likely
to press a lever to self-administer cocaine, and received fewer
self-initiated infusions of the drug following eight months of treatment
than the lower-dose group or the control rats.

The changes observed in brain chemistry were specific to the age and
duration of methylphenidate treatment: Specifically, after two months of
treatment, brain scans revealed that both groups of treated rats had lower
levels of dopamine D2 receptors in their brains than did control animals.

In contrast, after eight months of treatment, the brain scans revealed
elevated levels of dopamine D2 receptors in treated rats compared with
controls, with the higher-dose treatment group showing the highest level of
D2 receptors. In the control group, D2 receptor levels declined with age.

Research at Brookhaven and elsewhere has suggested that low levels of
dopamine D2 receptors may increase the likelihood of drug abuse, while
elevated levels of dopamine D2 receptors may attenuate the propensity to
abuse drugs.

"This new study provides evidence that chronic methylphenidate treatment
begun in adolescence affects the brain's dopamine D2 receptor levels, and
thus the brain's reward circuitry, differently depending on the age and
treatment duration," Thanos said. The scientists' observation of lower rates
of cocaine self-administration in the animals treated for eight months with
a 2kg/mg dose of methylphenidate supports this idea.

However, the observation of lower levels of D2 receptors after two months of
treatment suggests that shorter lengths of treatment or the age at which
treatment is evaluated could result in different effects. "Lower dopamine D2
receptor levels following short-term treatment could make the animals more
vulnerable to drug self-administration during early adulthood," Thanos said.
"Unfortunately, we cannot compare cocaine self-administration following
eight months of treatment with that obtained after two months of treatment
in the same animals, since animals were not tested for cocaine
self-administration at this earlier time," Thanos said. "We wanted to avoid
any confounding effect that might have resulted from cocaine exposure during
this early developmental stage," he explained.

Evaluating the effect of treatment duration is one avenue the researchers
are exploring in follow-up studies "to help assess optimal duration of
treatment regimes to minimize adverse effects on the propensity to abuse
drugs," Thanos said.

Thanos notes that the findings from this study cannot be directly
extrapolated to treatment regimes used for ADHD. Also, these studies were
done in healthy animals, not in rodent models of ADHD. All experiments were
conducted in conformity with the National Academy of Sciences Guide for Care
and Use of Laboratory Animals and Brookhaven National Laboratory
Institutional Animal Care and Use Committee protocols.

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This research was funded by the National Institute on Alcohol Abuse and
Alcoholism intramural program and by the Office of Environmental and
Biological Research within the U.S. Department of Energy's Office of
Science.

One of ten national laboratories overseen and primarily funded by the Office
of Science of the U.S. Department of Energy (DOE), Brookhaven National
Laboratory conducts research in the physical, biomedical, and environmental
sciences, as well as in energy technologies and national security.
Brookhaven Lab also builds and operates major scientific facilities
available to university, industry and government researchers. Brookhaven is
operated and managed for DOE's Office of Science by Brookhaven Science
Associates, a limited-liability company founded by the Research Foundation
of State University of New York on behalf of Stony Brook University, the
largest academic user of Laboratory facilities, and Battelle, a nonprofit,
applied science and technology organization.

Contact: Karen McNulty Walsh
DOE/Brookhaven National Laboratory