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Leptin ProtectsAgainst theDevelopment andExpression of CocaineAddiction-LikeBehavior inHeterogeneous StockRats Lieselot L. G. CarretteC. Cano CorralBrent Boomhower2022 год

Leptin Protects Against the Development and Expression of Cocaine Addiction-Like Behavior in Heterogeneous Stock Rats
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Аннотация: Cocaine affects food intake, metabolism and bodyweight. It has been hypothesized that feeding hormones like leptin play a role in this process. Preclinical studies have shown a mutually inhibitory relationship between leptin and cocaine, with leptin also decreasing the rewarding effects of cocaine intake. But prior studies have used relatively small sample sizes and did not investigate individual differences in genetically heterogeneous populations. Here, we examined whether the role of individual differences in bodyweight and blood leptin level are associated with high or low vulnerability to addiction-like behaviors using data from 306 heterogeneous stock rats given extended access to intravenous self-administration of cocaine and 120 blood samples from 60 of these animals, that were stored in the Cocaine Biobank. Finally, we tested a separate cohort to evaluate the causal effect of exogenous leptin administration on cocaine seeking. Bodyweight was reduced due to cocaine self-administration in males during withdrawal and abstinence, but was increased in females during abstinence. However, bodyweight was not correlated with addiction-like behavior vulnerability. Blood leptin levels after ∼6 weeks of cocaine self-administration did not correlate with addiction-like behaviors, however, baseline blood leptin levels before any access to cocaine negatively predicted addiction-like behaviors 6 weeks later. Finally, leptin administration in a separate cohort of 59 animals reduced cocaine seeking in acute withdrawal and after 7 weeks of protracted abstinence. These results demonstrate that high blood leptin level before access to cocaine may be a protective factor against the development of cocaine addiction-like behavior and that exogenous leptin reduces the motivation to take and seek cocaine. On the other hand, these results also show that blood leptin level and bodyweight changes in current users are not relevant biomarkers for addiction-like behaviors.
Год издания: 2022
Авторы: Lieselot L. G. Carrette, C. Cano Corral, Brent Boomhower, Molly Brennan, Caitlin Crook, Clara A. Ortez, Kokila Shankar, Sierra Simpson, Lisa Maturin, Leah C. Solberg Woods, Abraham A. Palmer, Giordano de Guglielmo, Olivier George
Издательство: Frontiers Media
Источник: Frontiers in Behavioral Neuroscience
Ключевые слова: Regulation of Appetite and Obesity, Biochemical Analysis and Sensing Techniques, Adipokines, Inflammation, and Metabolic Diseases
Другие ссылки: Frontiers in Behavioral Neuroscience (PDF)
Frontiers in Behavioral Neuroscience (HTML)
DOAJ (DOAJ: Directory of Open Access Journals) (HTML)
eScholarship (California Digital Library) (PDF)
eScholarship (California Digital Library) (HTML)
PubMed Central (HTML)
PubMed (HTML)