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Drug-seeking motivation level in male rats determines offspring susceptibility or resistance to cocaine-seeking behaviour.

ABSTRACT: Liability to develop drug addiction is heritable, but the precise contribution of non-Mendelian factors is not well understood. Here we separate male rats into addiction-like and non-addiction-like groups, based on their incentive motivation to seek cocaine. We find that the high incentive responding of the F0 generation could be transmitted to F1 and F2 generations. Moreover, the inheritance of high incentive response to cocaine is contingent on high motivation, as it is elicited by voluntary cocaine administration, but not high intake of cocaine itself. We also find DNA methylation differences between sperm of addiction-like and non-addiction-like groups that were maintained from F0 to F1, providing an epigenetic link to transcriptomic changes of addiction-related signalling pathways in the nucleus accumbens of offspring. Our data suggest that highly motivated drug seeking experience may increase vulnerability and/or reduce resistance to drug addiction in descendants.

SUBMITTER: Le Q

PROVIDER: S-EPMC5459992 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Drug-seeking motivation level in male rats determines offspring susceptibility or resistance to cocaine-seeking behaviour.

Le Qiumin Q Yan Biao B Yu Xiangchen X Li Yanqing Y Song Haikun H Zhu Huiwen H Hou Weiqing W Ma Dingailu D Wu Feizhen F Zhou Yuqing Y Ma Lan L

Nature communications 20170530

Liability to develop drug addiction is heritable, but the precise contribution of non-Mendelian factors is not well understood. Here we separate male rats into addiction-like and non-addiction-like groups, based on their incentive motivation to seek cocaine. We find that the high incentive responding of the F0 generation could be transmitted to F1 and F2 generations. Moreover, the inheritance of high incentive response to cocaine is contingent on high motivation, as it is elicited by voluntary c ...[more]

PMID: 28556835

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Project description:BackgroundAlcohol use disorder is one of the most common psychiatric disorders, and it is a leading cause of mortality worldwide. It has been demonstrated previously that people with alcohol use disorder are less sensitive to the negative outcomes of their actions and less able to use negative feedback to guide and adjust their ongoing behaviour. However, far less is known about the aberrant processing of negative feedback before the onset of alcohol use disorder. In this study, we investigated the theoretical claim that sensitivity to negative feedback - as a stable and enduring behavioural trait - can predict vulnerability to the development of compulsive alcohol consumption in rats.MethodsWe trained and tested rats in a series of probabilistic reversal learning tests, and based on this "negative feedback sensitivity screening," we classified each rat as more or less sensitive to negative feedback. Then, in the intermittent-access 2-bottle choice paradigm, we measured alcohol consumption in the animals classified above. In the next step, using the instrumental second-order chained schedule of alcohol reinforcement task, we examined the influence of sensitivity to negative feedback on the development of compulsive alcohol seeking behaviour. Finally, we measured how trait sensitivity to negative feedback affected the extinction and reinstatement of alcohol seeking after a period of abstinence.ResultsTrait sensitivity to negative feedback predicted the vulnerability of rats to the development of compulsive alcohol seeking and consumption. We also found significant differences between the more sensitive and less sensitive groups in their propensity to extinguish alcohol seeking behaviours when the alcohol was no longer available.LimitationsThe findings from our study did not answer the question of whether individual differences in sensitivity to negative feedback have a genetic basis or develop in response to postnatal experiences.ConclusionThe results of our study suggest that negative feedback sensitivity screening could be used to evaluate individual vulnerability to the development and maintenance of alcohol use disorder.

Dataset Information

Drug-seeking motivation level in male rats determines offspring susceptibility or resistance to cocaine-seeking behaviour.

Publications

Drug-seeking motivation level in male rats determines offspring susceptibility or resistance to cocaine-seeking behaviour.

Similar Datasets

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