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Multiple elements of addiction vulnerability are independently heritable in rats

Maya Eid, Dominika Pullmann, Hao Li, Alen Thomas, Thomas C. Jhou
doi: https://doi.org/10.1101/566018
Maya Eid
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Dominika Pullmann
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Hao Li
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Alen Thomas
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Thomas C. Jhou
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ABSTRACT

Background Although cocaine is powerfully rewarding, only a fraction of drug-exposed individuals actually transition to become drug-dependent users, possibly due in part to genetic influences, as addictions are among the most heritable of human neuropsychiatric disorders. Consistent with addiction being a complex disorder, prior studies have noted many factors that predict addiction vulnerability, such as drug-induced aversive effects, behavioral responses to novelty, and sensitivity to punishment.

Methods We tested different inbred strains of rats, as well as selectively bred Sprague-Dawley (SD) or Heterogeneous Stock (HS) rats, on cocaine avoidance, sensitivity to punishment, and locomotor responses to novelty, and calculated heritability estimates of these behaviors. We tested animals on additional control tasks (progressive ratio, shock avoidance) to control for alternate interpretations of addiction-like behaviors.

Results Conditioned avoidance to cocaine varied greatly between individual rats as measured using either the runway operant task or conditioned place aversion (CPA). Cocaine avoidance responded rapidly to selective breeding, yielding heritability estimates of 0.70 and 0.58 in SD and HS rats. Resistance to punishment was also highly heritable in inbred rats (estimated h2 = 0.62), and varied independently of cocaine avoidance despite both behaviors being mediated by the RMTg. Furthermore, cocaine avoidance correlated positively with cocaine-induced c-Fos induction in the RMTg, negatively with initial rates of acquisition of intravenous cocaine self-administration, and positively with both cued and cocaine-primed reinstatement.

Conclusions Cocaine avoidance and resistance to punishment are strongly and independently heritable behaviors that may both control different aspects of individual propensity to acquire and maintain drug-seeking.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 04, 2019.
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Multiple elements of addiction vulnerability are independently heritable in rats
Maya Eid, Dominika Pullmann, Hao Li, Alen Thomas, Thomas C. Jhou
bioRxiv 566018; doi: https://doi.org/10.1101/566018
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Multiple elements of addiction vulnerability are independently heritable in rats
Maya Eid, Dominika Pullmann, Hao Li, Alen Thomas, Thomas C. Jhou
bioRxiv 566018; doi: https://doi.org/10.1101/566018

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