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A genetic reduction in the serotonin transporter differentially influences MDMA and heroin induced behaviours

Abstract

Background

Despite ongoing study and research to better understand drug addiction, it continues to be a heavy burden. Only a small percentage of individuals who take drugs of abuse go on to develop addiction. However, there is growing evidence to suggest that a reduction in the serotonin transporter may play an important role for those that transition to compulsive drug taking. Studies have demonstrated that reduced serotonin transporter function potentiates self-administration of psychostimulant drugs (“ecstasy,” MDMA; cocaine); however, additional research revealed no differences between genotypes when the opioid heroin was self-administered. These results suggest that a reduction in the serotonin transporter may confer susceptibility to the development of addiction to some classes of drugs but not others. Importantly, the mechanism underlying facilitated psychostimulant self-administration is currently unknown.

Methods

Therefore, to continue investigating the relationship between compromised serotonergic function and different classes of drugs, a series of experiments was conducted investigating locomotor activity (LMA) and conditioned taste aversion (CTA) in the serotonin transporter knockout (SERT KO) rat model.

Results

MDMA-induced hyperactivity was reduced, while MDMA-induced CTA was enhanced, in SERT KO rats. However, there were no genotype differences in heroin-induced behaviours.

Conclusions

These results reinforce the idea that a reduction in the serotonin transporter drives differential effects between disparate classes of drugs of abuse.

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Acknowledgements

The authors would like to extend thanks to Mr. Richard Moore, Mr. Peter Van Compernolle and Mr. Michael Roberts for providing day-to-day husbandry, support and care of the animals used in these experiments. We would also like to thank Dr. Uta Waterhouse for providing assistance with the injections in the conditioned taste aversion experiments.

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Contributions

Bridget W. Brox contributed to this work by planning experiments, collecting data, data analysis and writing the first draft of this manuscript.

Bart A. Ellenbroek contributed to this work by advising in planning experiments, data analysis and supported the final revision of this manuscript.

Corresponding author

Correspondence to Bart A. Ellenbroek.

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Brox, B.W., Ellenbroek, B.A. A genetic reduction in the serotonin transporter differentially influences MDMA and heroin induced behaviours. Psychopharmacology 235, 1907–1914 (2018). https://doi.org/10.1007/s00213-018-4880-1

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Keywords

  • Serotonin
  • MDMA
  • Heroin
  • SERT