A genetic reduction in the serotonin transporter differentially influences MDMA and heroin induced behaviours.
Bridget W Brox, Bart A. Ellenbroek
Psychopharmacology July 2018 DOI: 10.1007/s00213-018-4880-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Serotonin transporter knockout (SERT KO) rats |
| Interventions | MDMA Heroin |
| Topics | MDMA Serotonin |
| Keywords | Heroin Sert |
| Key findings | In SERT knockout rats, MDMA-induced hyperactivity was reduced and MDMA-induced conditioned taste aversion was enhanced, whereas no genotype differences were found for heroin-induced behaviours. The authors argue this reinforces that reduced serotonin transporter function produces differential effects across classes of drugs of abuse. |
Abstract
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. 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. 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. These results reinforce the idea that a reduction in the serotonin transporter drives differential effects between disparate classes of drugs of abuse.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 3
- Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents Neuroscience & Biobehavioral Reviews September 20, 2024
- 3,4-Methylenedioxymethamphetamine (MDMA) does not induce robust psychomotor activation and 50-kHz ultrasonic vocalisations in tryptophan hydroxylase 2 (Tph2)-deficient rats lacking serotonin in the central nervous system. British Journal of Pharmacology November 23, 2025
- Methylone pre-exposure differentially impacts the aversive effects of MDPV and MDMA in male and female Sprague-Dawley rats: Implications for abuse vulnerability. Pharmacology, Biochemistry, and Behavior October 2022
Cites 7
- MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant? Frontiers in Genetics 2012
- Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”): The Influence of Gender and Genetics (CYP2D6, COMT, 5-HTT) PLoS One October 24, 2012
- Rats preexposed to MDMA display attenuated responses to its aversive effects in the absence of persistent monoamine depletions. Psychopharmacology August 2011
- Tolerance to 3,4-methylenedioxymethamphetamine is associated with impaired serotonin release. Addiction Biology May 11, 2010
- Effect of D1-like and D2-like receptor antagonists on methamphetamine and 3,4-methylenedioxymethamphetamine self-administration in rats. Behavioural Pharmacology December 2009
and 2 more in the library