Previous studies on the mechanism of addiction did not take into account the gender and impact of hormonal management on this process. As it turns out – this dependence is of great importance.
The study  that determined this relationship was performed on rats where drugs with a methamphetamine effect were used. Depending on rodens gender, a different degree of changes in the brain was observed in the direction of addiction mechanism formation [1, 4]. This is an interesting discovery that it can initiate a new type of therapy for people with addictions.
The scientists conducting the experiment suggest that the brains of male and female rats exposed in this case to methamphetamine react differently to intoxicants that lead to addictions. Probably these differences are the result of differences in the sex hormone economy between the sexes.
As a stimulant, methamphetamine increases the activity of individual brain centers, such as prefrontal cortex . Increases the production of dopamine in the brain, which allows you to achieve a feeling of fulfillment and pleasure. Often this action is called the “reward system”, which describes the accompanying feelings in a simple way. In addition, dopamine affects such parameters as motivation to act, the desire to physical activity, improves the process of memorizing and learning.
Due to the constantly high level of dopamine, people using methamphetamine affect the neuroplasticity of the brain in such a way that after a certain time it ceases to function normally on the standard amounts of dopamine produced by the body, which forces these people to increase the status of neurotransmitter stimulants. Exactly such changes were observed in all rats subjected to the cited study.
The researchers allowed the rats to self-administer doses of the drug, which means that the rats controlled the dose and the frequency of their consumption. After obtaining the status of addiction in rats, in the first 6 hours it was observed that the females consumed more methamphetamine and that these portions were more frequently consumed. Why was it that the females got this addicted? The answer is most likely the effect of sex hormones on brain actions.
Over time, the addiction mechanism changes the way the signals are transmitted by the brain, in particular the synapses in the prefrontal cortex, which is responsible for decision making and learning ability.
The results of the prefrontal cortex study of female and male rats that were addicted to methamphetamine and those who were not dependent showed differences in the synaptic response. The authors of the study noticed that female rats exhibited less resting activity than males, but then experienced a faster increase in brain synaptic activity (i.e. neurotransmitter delivery) after taking the drug. This was accompanied by a faster decrease in synaptic response after discontinuation of the substance.
It was noticed that the methamphetamine supply evoked noticeably greater changes in the NMDA receptor kinetics (NMDAR, glutamate activated receptors) and the increase in pulses transmitted by them. Inhibition of NMDAR selective activity with GluN2B blocker (type of NMDA receptor subunit, affecting the nerve signal strength ) did not change anything. This suggests that the mechanism of addiction formation results from changes in synaptic functions.
„[…] and analysis of the NMDA current kinetics shows that, in contrast to males, the GluN2B blocker did not affect the kinetics of NMDA currents in METH SA females. […]” .
The researchers also suggest that there is a dose-dependent threshold for the formation of negative changes in synaptic plasticity and it’s gender-dependent.
What is the mechanism?
Researchers are not sure, but they say that AMPAR (glutamate subunits) in the area of the cerebral cortex increase the extracellular concentration of dopamine, where NMDAR activation decreases it. Differences that occur in females and males in the area of NMDAR activation may result from a pool of total androgens. it’s speculated that the administration of methamphetamine induces an increase in the release of dopamine, which in women is synergistic with the lack of androgens and causes an increase in NMDA activity.
These reports must be supported by further research, but they may trigger a new mechanism of therapy in the fight against addictions.
- Jose Ignacio Pena-Bravo, Rachel Penrod, Carmela M. Reichel and Antonieta Lavin. Methamphetamine Self-Administration Elicits Sex-Related Changes in Postsynaptic Glutamate Transmission in the Prefrontal Cortex. eNeuro 10 January 2019, 6 (1) ENEURO.0401-18.2018; DOI: https://doi.org/10.1523/ENEURO.0401-18.2018
- Joana S Ferreira, Thomas Papouin, Laurent Ladépêche, Andrea Yao, Valentin C Langlais, Delphine Bouchet,1Jérôme Dulong, Jean-Pierre Mothet, Silvia Sacchi, Loredano Pollegioni, Pierre Paoletti, Stéphane Henri Richard Oliet, and Laurent Groc. Co-agonists differentially tune GluN2B-NMDA receptor trafficking at hippocampal synapses. eLife. 2017; 6: e25492. Published online 2017 Jun 9. doi: 10.7554/eLife.25492
- Twum Ampofo Ansah, Marcus Ferguson, and Tultul Nayyar. Effects of strain on MDMA (“ecstasy”)-induced locomotor hyperactivity and sensitization in mice. Faseb Journal. Vol. 22, No. 1_supplement March 2008