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Guess, K.

Publications and source records attributed to Guess, K..

2 recordsLinked to original sources

Sex-specific competitive social feedback amplifies the role of early life contingency in male mice

Contingency (or luck) in early life plays an important role in shaping individuals development. When individuals live within larger societies, social experiences may cause the importance of early contingencies to be magnified or dampened. Here we test the hypothesis that competition magnifies the importance of early contingency in a sex-specific manner by comparing the developmental trajectories of genetically identical, free-living mice who either experienced high levels of territorial competition (males) or did not (females). We show that male territoriality results in a competitive feedback loop that magnifies the importance of early contingency and pushes individuals onto divergent, self-reinforcing life trajectories, while the same process appears absent in females. Our results indicate that the strength of sexual selection may be self-limiting, as within-sex competition increases the importance of early life contingency, thereby reducing the ability of selection to lead to evolution. They also demonstrate the potential for contingency to lead to dramatic differences in life outcomes, even in the absence of any underlying differences in ability ( merit).

evolutionary biology↗

Individual differences in oxycodone addiction-like behaviors in a large cohort of heterogeneous stock (HS) rats

Family and twin studies demonstrate that genetic factors determine 20-60% of the vulnerability to opioid use disorder. However, the genes/alleles that mediate the risk of developing addiction-related behaviors, including the sensitivity to the analgesic efficacy of opioids, the development of tolerance, dependence, and escalation of oxycodone taking and seeking, have been ill-defined, thus hindering efforts to design pharmacological interventions to enable precision medicine strategies. Here we characterized oxycodone addiction-like behaviors in heterogeneous stock (HS) rats, that show high genetic diversity that mimics the high genetic variability in humans. HS rats were allowed to self-administer oxycodone for two h/daily for four days (ShA) and then moved to 12h/daily (LgA) for 14 days. Animals were screened for motivation to self-administer oxycodone using a progressive-ratio (PR) schedule of reinforcement and for the development of withdrawal-induced hyperalgesia and tolerance to the analgesic effects of oxycodone using the von-Frey and tail immersion tests, respectively. To reduce cohort-specific effects, we used cohorts of 46-60 rats and normalized the response level within cohorts using a Z-score. To take advantage of the four opioid-related behaviors and further identify subjects that are consistently vulnerable vs. resilient to compulsive oxycodone use, we computed an Addiction Index by averaging normalized responding (Z-scores) for the four behavioral tests. Results showed high individual variability between vulnerable and resilient rats, likely to facilitate the detection of gene variants associated with vulnerable vs. resilient individuals. Such data will have considerable translational value for designing follow-up studies in humans.

neuroscience↗