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bioRxiv · 10.1101/2025.07.10.664140

Novel reactivity phenotype mediates long-term consequences of cocaine exposure during adolescence and adulthood in male Sprague-Dawley rats.

Maldonado-Devincci, A. M.·Amante, R. A.·Raudales, R.·Micheal, L. A.·Badanich, K. A.·Kirstein, C. L.
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Abstract

Individual differences in novelty seeking behavior often predict locomotor responses to psychomotor stimulants, an effect that may have a lasting impact throughout adolescence. The present study examined the role of novel reactivity phenotype on locomotor responses to repeated cocaine exposure during adolescence and adulthood in male rats. Prior to drug exposure, reactivity to a novel object was measured and animals were separated into low responders (LR) and high responders (HR). Cocaine was administered daily (0 or 20 mg/kg, i.p.) for 12 consecutive days, and behavior recorded on days 1, 6, and 12. After 28 days without drug, rats were challenged with cocaine (20 mg/kg) and behavior was assessed. Novel reactivity phenotype had a dramatic role in adolescents acute responsiveness to cocaine. HR adolescents exhibited a robust increase in sensitivity to acute administration of 20 mg/kg cocaine. However, following repeated cocaine exposure, both LR and HR adults displayed a marked increase in cocaine-induced locomotor activity, whereas the change in behavioral responsiveness in LR and HR adolescents was not as dramatic. During the cocaine challenge trial, LR that were exposed to 20 mg/kg cocaine during adolescence showed the highest cocaine-induced responsiveness compared to their saline-exposed and adult-exposed counterparts. Overall, these data indicate that novel reactivity phenotype and age of initial cocaine exposure are intricately involved in the long-term behavioral effects of cocaine. Thus, novel reactivity phenotype may predispose cocaine-using adolescents to continue drug-seeking behavior and potential abuse. HighlightsO_LINovel reactivity is higher in adolescents compared to adults C_LIO_LIAdolescents show greater acute cocaine-induced activity compared to adults C_LIO_LIHigh responding adolescents show robust acute cocaine-induced activity C_LIO_LILow responding adolescents show lasting changes in cocaine activity in adulthood C_LI

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Maldonado-Devincci, A. M., Amante, R. A., Raudales, R., Micheal, L. A., Badanich, K. A., Kirstein, C. L.. 2025-07-15. Novel reactivity phenotype mediates long-term consequences of cocaine exposure during adolescence and adulthood in male Sprague-Dawley rats.. https://doi.org/10.1101/2025.07.10.664140

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