Alcohol potentiates the neurochemical, psychostimulant and addictive effects of mephedrone.
Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
The increasing use of synthetic cathinones, such as mephedrone, could exacerbate the risk of suffering both addictive as well as neurochemical effects. Given the increasing popularity of this b-ketoamphetamine and its pattern of use, it is essential to evaluate if additional health risks are involved when combined with alcohol given that up to date there are no published studies looking specifically at mephedrone and alcohol in combination.The aim of this study was to look into a possible potentiation of the initial neurochemical effects due to mephedrone after using it in combination with alcohol. This was carried out using a combined ethanol and mephedrone treatment schedule that we hypothesizes would exert some form of neurochemical effect in mice; findings were supported by protein extraction, western blot immunodetection and radioligand binding studies.Another approach in this project was to elucidate whether alcohol is able to enhance the addictive potential of mephedrone. This was carried out using an addiction behavioral study (Conditioned Place Preference, CPP). We finally also performed a combined ethanol and mephedrone treatment schedule in order to elucidate if ethanol could modify mephedrone‟s psychostimulant effect in mice. This was evidenced using an actimeter.The radioligand binding studies showed that the combination of mephedrone and ethanol reduces serotonin (5-HT) transporters (SERT) in hippocampus significantly in comparison to all other groups, indicating that the amount of functional serotonergic terminals decreases when administrating them concomitantly to a greater extent than each one separately. The results also indicated that the amount of dopamine transporters (DAT) in cortex is reduced in a significant manner after the concomitant administration when compared to saline or ethanol control groups. No statistically significant differences were seen between the concomitant administration and the mephedrone groups alone but a very clear tendency towards a decrease in DAT could be observed. The results from the western blot immunodetection showed consistency with the binding to DAT in cortex when performing t-test comparisons between groups.It seems clear that alcohol is able to enhance the addictive potential of mephedrone in the CPP test when comparing to the mephedrone groups alone, although statistically significant results were not obtained from this study. The psychostimulant study using an actimeter and locomotoractivity box showed significant differences in AUC when comparing the concomitant administration to all other groups, indicating that ethanol can enhance the psychostimulant effect of mephedrone.
Place, publisher, year, edition, pages
2013. , 16 p.
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:uu:diva-214563OAI: oai:DiVA.org:uu-214563DiVA: diva2:685082
Subject / course
Master of Science Programme in Pharmacy
2013-06-03, Sal: B8:001, BMC, Husargatan 3, Uppsala, 13:20 (Swedish)
Pubill, David, Professor
Bergström, Lena, Universitetslektor