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Adolescent exposure to sucrose increases cocaine‐mediated behaviours in adulthood via Smad3

Title: Adolescent exposure to sucrose increases cocaine‐mediated behaviours in adulthood via Smad3
Authors: Gancarz, Amy M.; Parmar, Raveena; Shwani, Treefa; Cobb, Moriah M.; Crawford, Michelle N.; Watson, Jacob R.; Evans, Lisa; Kausch, Michael A.; Werner, Craig T.; Dietz, David M.
Contributors: National Institute of General Medical Sciences; National Institutes of Health
Source: Addiction Biology ; volume 28, issue 12 ; ISSN 1355-6215 1369-1600
Publisher Information: Wiley
Publication Year: 2023
Collection: Wiley Online Library (Open Access Articles via Crossref)
Description: Adolescence, a critical period of developmental period, is marked by neurobiological changes influenced by environmental factors. Here, we show how exposure to sucrose, which is ubiquitously available in modern diets, results in changes in behavioural response to cocaine as an adult. Rats were given daily access to either 10% sucrose or water during the adolescent period (PND28–42). Following this period, rats are left undisturbed until they reach adulthood. In adulthood, rats were tested for (i) acquisition of a low dose of cocaine, (ii) progressive ratio (PR) test, and (iii) resistance to punished cocaine taking. Sucrose exposure resulted in significant alterations in all behavioural measures. To determine the neurobiological mechanisms leading to such behavioural adaptations, we find that adolescent sucrose exposure results in an upregulation of the transcription factor Smad3 in the nucleus accumbens (NAc) when compared with water‐exposed controls. Transiently blocking the active form of this transcription factor (HSV‐dnSmad3) during adolescence mitigated the enhanced cocaine vulnerability‐like behaviours observed in adulthood. These findings suggest that prior exposure to sucrose during adolescence can heighten the reinforcing effects of cocaine. Furthermore, they identify the TGF‐beta pathway and Smad3 as playing a key role in mediating enduring and long‐lasting adaptations that contribute to sucrose‐induced susceptibility to cocaine. Taken together, these results have important implications for development and suggest that adolescent sucrose exposure may persistently enhance the susceptibility to substance abuse.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1111/adb.13346
Availability: https://doi.org/10.1111/adb.13346; https://onlinelibrary.wiley.com/doi/pdf/10.1111/adb.13346
Rights: http://creativecommons.org/licenses/by-nc-nd/4.0/
Accession Number: edsbas.AEC2A79C
Database: BASE