Gender differences in the interaction of cathinone with caffeine on cardiovascular and central responses

[Speaker] James R Docherty:1
[Co-author] Hadeel A Alsufyani:2
1:Physiology, Royal College of Surgeons in Ireland, Ireland, 2:Physiology, King Abdulaziz University, Jeddah, Saudi Arabia

Cathinone is a beta-keto-amphetamine from Khat (Catha edulis Forsk) and has MDMA-like actions (Kalix, 1990) that are largely indirect by release of monoamines (Alsufyani & Docherty 2015). Khat users often combine coffee with the stimulant causing possible interactions.
We have investigated gender differences in the effects of cathinone (the major stimulant from Khat) and the interaction with caffeine on cardiovascular and activity and temperature responses in Wistar rats. In pentobarbitone-anaesthetised rats cathinone produced marked tachycardia and small pressor responses. The cardiac and pressor responses to both cathinone and MDMA were unaffected by caffeine and there were no gender differences. In animals implanted 7 days before with telemetry probes under isoflurane anaesthesia sampling was commenced and caffeine (10 mg/kg) or vehicle injected subcutaneously at 5 min. 30 min later cathinone (5 mg/kg) or vehicle were injected subcutaneously.
Caffeine alone produced only small increases in total activity but even these small effects were significantly greater in female rats (one way Anova of total activity P<0.05). Cathinone produced marked increases in activity and the response to cathinone was significantly greater in female animals. The combination of caffeine and cathinone causes a short lived potentiation followed by a prolonged inhibition of the activity response to cathinone. Cathinone alone had minor effects on temperature in male animals and produced small slowly developing rises in female animals. However the combination of caffeine and cathinone produced a significant acute rise in temperature only in male rats.
In conclusion the peak activity response cathinone was significantly increased but the later response was significantly reduced, by the presence of caffeine especially in female rats. Cathinone caused greater increases in activity in female than in male rats and in combination with caffeine significantly raised temperature acutely in male but not female rats. These differences highlight the need to carry out gender studies of the actions of stimulants

Alsufyani HA Docherty JR (2015). Eur J Pharmacol 758: 142-146
Kalix P (1990) Pharmacol Ther 48:397-416.

Supported by King Abdelaziz University Jeddah KSA
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