GENDER DIFFERENCES IN THE INTERACTION OF CATHINONE WITH CAFFEINE ON LOCOMOTOR ACTIVITY IN THE RAT

Leaves of Khat (Catha edulis Forsk) contain the β‐keto‐amphetamine cathinone that has MDMA‐like actions (Kalix, 1990). The actions of cathinone are largely indirect by release of monoamines to act both centrally and peripherally (Alsufyani & Docherty, 2015). Gender differences occur in the use and effects of stimulants, including Khat, in humans, but in basic research, female animal models have been rarely studied. We have investigated gender differences in the effects of cathinone (the major stimulant from Khat) and the interaction with caffeine on locomotor activity in Wistar rats. Indeed, Khat users often combine coffee with the stimulant. Animals were implanted with telemetry probes under isoflurane anaesthesia, and 7 days later, locomotor activity was recorded in conscious unrestrained animals. Following an equilibration period, sampling was commenced and at 5 min, caffeine (10 mg/kg) or vehicle, and 30 min later, cathinone (5 mg/kg) or vehicle were injected subcutaneously in male and female rats. Recording continued for a further 240 min. Time course of effects was investigated at 5 min intervals. Caffeine alone produced only small increases in total locomotor activity, but even these small effects were significantly greater in female rats (one way Anova of total activity over the whole sampling period, P<0.05). Cathinone produced significant and marked increases in locomotor activity, beginning soon after injection, and the response to cathinone was significantly greater in female animals (two way Anova of time course of effect, P<0.05). The combination of caffeine and cathinone causes a transient potentiation, followed by a prolonged inhibition, of the locomotor response to cathinone. Hence, the peak response to injection of cathinone was significantly increased, but for much of the next 120 min, the response to cathinone was significantly reduced by the presence of caffeine, especially in female rats. In conclusion, cathinone causes greater increases in locomotor activity in female than in male rats, but although the acute effects of cathinone are potentiated by caffeine, the maintained effects of cathinone on locomotor activity are, perhaps surprisingly, reduced by caffeine in both male and female rats. These differences highlight the need to carry out gender studies of the actions and interactions of stimulants in basic studies. Alsufyani HA, Docherty JR (2015). Eur J Pharmacol 758: 142–146 Kalix P (1990) Pharmacol Ther, 48:397–416. Support or Funding Information HAA is funded by a scholarship from the Saudi Government Ministry of Higher Education, KAU.