Dopaminergic Nature of Acute Cathine Tolerance

Cathine is a psychoactive constituent in the leaves of the Khat shrub which are habitually ingested for their stimulatory effects in many parts of the world. Rats were trained to discriminate the stimulus effect of intraperitoneally administered 4.8 mg/kg d-cathine and, once trained, administration of another Khat constituent, cathinone, was shown to produce cathine-like effects. This generalization to cathinone was dose-responsive when testing occurred 24 hr after vehicle administration, whereas prior administration of cathine resulted in a diminished discriminative response to subsequent cathinone administration possibly as a result of the development of acute tolerance. CGS 10746B, a compound that blocks presynaptic release of dopamine, significantly decreased rats' ability to discriminate cathine when it was administered 25 min prior to cathine testing and it reversed the acute tolerance observed when cathine was tested 24 hr after cathine administration. These results indicate that a previously reported acute tolerance effect to cathine after cathinone administration in cathinone-trained rats appears to be symmetrical in that there is acute tolerance to cathinone after cathine in these cathine-trained rats. The results with CGS 10746B would suggest that both the cathine-induced discriminative cue and cathine's ability to produce acute tolerance are mediated by presynaptic dopamine release.