Rats become acutely tolerant to cathine after amphetamine or cathinone administration.
Male; Animals; Rats; Drug Tolerance; Discrimination (Psychology)/drug effects; Psychotropic Drugs/*pharmacology; Thiazepines/pharmacology; Antipsychotic Agents/pharmacology; Alkaloids/*pharmacology; Amphetamine/*pharmacology; Phenylpropanolamine/*pharmacology; Dose-Response Relationship; Drug; Inbred Strains
The drug discrimination paradigm was used to evaluate in rats the ability of the discriminate response to either 0.8 mg/kg d-amphetamine or 0.8 mg/kg l-cathinone to generalize to 2.4-6.0 mg/kg of the active cathinone metabolite d-norpseudoephedrine, also known as cathine. When tested 24 h after vehicle administration, cathine generalized in a dose-related fashion in rats (n = 6) trained with cathinone (ED50 = 3.03 mg/kg) and in rats (n = 8) trained with amphetamine (ED50 = 2.93 mg/kg). In contrast, when cathine was tested 24 h after the administration of either amphetamine or cathinone, it produced significantly decreased discriminative performance. The possibility that this acute tolerance may have been produced by release, and subsequent depletion, of brain dopamine was tested by pretreating rats with the dopamine release inhibitor CGS 10746B. When CGS 10746B was administered prior to cathinone it significantly decreased cathinone discrimination. In addition, acute tolerance to cathine at 24 h after vehicle-cathinone co-administration was reversed when cathine was tested 24 h after CGS 10746B-cathinone co-administration. The results suggest that cathinone-produced discriminative stimulus, as well as the acute tolerance to cathine, may be dopaminergically mediated.
Schechter M D
Psychopharmacology
1990
1905-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/bf02253729" target="_blank" rel="noreferrer noopener">10.1007/bf02253729</a>
Dopaminergic nature of acute cathine tolerance.
Male; Animals; Rats; Drug Tolerance; Dopamine/*physiology; Discrimination (Psychology)/drug effects; Discrimination Learning/drug effects; Alkaloids/pharmacology; Thiazepines/pharmacology; Antipsychotic Agents/pharmacology; Appetite Depressants/*pharmacology; Phenylpropanolamine/*pharmacology; Generalization (Psychology)/drug effects; Dose-Response Relationship; Drug; Inbred Strains
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.
Schechter M D
Pharmacology, biochemistry, and behavior
1990
1990-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0091-3057(90)90083-t" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(90)90083-t</a>