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[Abstract Title]. - Society for Neuroscience

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Poster<br />

291. Animal Cognition and Behavior: Learning and Memory: Pharmacology II<br />

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm<br />

Program#/Poster#: 291.22/SS5<br />

Topic: F.02.j. Learning and memory: Pharmacology<br />

Support: SENACYT Grant FID06-001<br />

<strong>Title</strong>: Long-term exposure to clinically relevant doses of oral methylphenidate has enduring<br />

effects on emotional behaviors in rats<br />

Authors: J. A. BETHANCOURT 1,2 , Z. Z. CAMARENA 1,2 , C. B. SALAZAR 3 , G. C.<br />

QUINTERO 1 , *G. B. BRITTON 1 ;<br />

1 Cognición, Cerebro y Conducta, INDICASAT, Panama, Panama; 2 Facultad de Psicología, Univ.<br />

de Panamá, Panamá, Panama; 3 Facultad de Psicología, Univ. Católica Santa María la Antigua,<br />

Panamá, Panama<br />

<strong>Abstract</strong>: Methylphenidate (MPH) is the most commonly prescribed psychostimulant used in<br />

the treatment of symptoms associated with attention-deficit/hyperactivity disorder (ADHD) in<br />

children, adolescents and adults. Despite its widespread use, general safety and effectiveness, a<br />

rising concern involves its potential to modify neural developmental processes that take place<br />

during pre- and peri-adolescence and to produce enduring changes in neural structure and<br />

function. Behavioral studies have shown that rats treated with MPH during early developmental<br />

periods exhibit cognitive and emotional deficits in adulthood, presumably due to long-lasting<br />

effects of MPH on maturing dopaminergic systems. Whether the therapeutic benefits of MPH<br />

outweigh its effects on neurobehavioral processes remains unknown. Because a growing<br />

proportion of adolescents continue MPH use into young adulthood, the present study examined<br />

the long-term effects of MPH administration from early developmental periods through<br />

adulthood on emotional and cognitive behaviors, and spontaneous locomotion and exploration.<br />

Peri-adolescent Wistar rats (beginning at post-natal day 28) were treated twice daily with MPH<br />

(2, 3 or 5 mg/kg) <strong>for</strong> seven weeks using an oral administration procedure that parallels clinical<br />

practice (weekdays only). Two weeks following the last drug treatment, animals were tested over<br />

a five-week period on a battery of procedures including the open field, novel object recognition,<br />

light-dark transition, elevated plus maze, and fear conditioning paradigms. We found that rats<br />

exposed to 3 or 5 mg/kg exhibited increases in anxiety-related behaviors measured in the open<br />

field, light-dark transition, and fear conditioning tests, but no deficits were observed in<br />

locomotion or exploration, or in the object recognition test at short or long retention intervals.<br />

These results are a first demonstration that MPH administration from juvenile periods through<br />

adulthood at clinically relevant doses has enduring effects on emotional responding without

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