Titre du document / Document title

Contribution of the active metabolite, norcocaine, to cocaine's effects after intravenous and oral administration in rats : pharmacodynamics

Auteur(s) / Author(s)

WANG Q. ⁽¹⁾ ; SIMPAO A. ⁽¹⁾ ; SUN L. ⁽¹⁾ ; FALK J. L. ⁽¹⁾ ; LAU C. E. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Psychology, Rutgers, The State University of New Jersey, 152 Frelinghuysen Road, Piscataway, NJ 08854-8020, ETATS-UNIS

Résumé / Abstract

Rationale: Oral cocaine is more effective than IV cocaine by pharmacokinetic and pharmacodynamic analysis. One explanation is involvement of the active metabolite, norcocaine, in cocaine's effects. Objectives: To evaluate norcocaine's contribution to oral cocaine's effects, norcocaine's effects as a parent compound were determined and compared to those of cocaine using a differential reinforcement of low rate (DRL 45-s) schedule and spontaneous activity (large and small movements) after IV and PO routes of administration. Methods: The effects of cocaine and norcocaine on DRL performance (shorter-response and reinforcement rates) and spontaneous activity were investigated in 3-h sessions. The changes in effects across time (effect-time profiles) and dose-response curves (DRCs) were constructed to evaluate the duration of action and potency (ED₅₀) of both drugs. Results: Under the DRL 45-s schedule, effect-time profiles showed both drugs via the two routes of administration significantly increasing and decreasing shorter-response rates and reinforcement rates, respectively. However, cocaine produced greater effects on shorter-response rates than norcocaine, while both drugs produced comparable effects on reinforcement rates. For spontaneous activity, although IV cocaine, PO cocaine, and PO norcocaine dose- and time-dependently increased spontaneous activity, cocaine's effects were more profound than those of norcocaine. Effect-time profiles revealed that the duration of drug action was a function of dose, route, and behavioral paradigm used. According to ED₅₀ values, IV cocaine was more effective than PO cocaine; however, PO cocaine was more effective than IV cocaine as judged by ED₅₀ values corrected for absolute oral bioavailability. Conclusions: Norcocaine's contribution to oral cocaine's effects on DRL performance is evident. Other mechanism(s), such as a greater acute tolerance to IV cocaine's effects than to PO cocaine's effects, can be excluded.

Revue / Journal Title

Psychopharmacologia   ISSN 0033-3158   CODEN PSYPAG 

Source / Source

2001, vol. 153, n^o3, pp. 341-352 (30 ref.)

Langue / Language

Anglais

Editeur / Publisher

Springer, Berlin, ALLEMAGNE  (1959) (Revue)

Mots-clés anglais / English Keywords

Cocaine ; CNS stimulant ; Psychotropic ; Drug of abuse ; Illicit drug ; Metabolite ; Toxicity ; Locomotion ; Spontaneous physical activity ; Reinforcement ; Pharmacokinetics ; Blood plasma ; Blood ; Pharmacokinetic pharmacodynamic relationship ; Instrumental conditioning ; Animal ; Rat ; Intravenous administration ; Oral administration ; Ester ; Dose activity relation ; Rodentia ; Mammalia ; Vertebrata ; Drug addiction ; Learning ; Acquisition process ;

Mots-clés français / French Keywords

Cocaïne ; Stimulant SNC ; Psychotrope ; Substance toxicomanogène ; Drogue illicite ; Métabolite ; Toxicité ; Locomotion ; Activité motrice spontanée ; Renforcement ; Pharmacocinétique ; Plasma sanguin ; Sang ; Relation pharmacocinétique pharmacodynamie ; Conditionnement instrumental ; Animal ; Rat ; Voie intraveineuse ; Voie orale ; Ester ; Relation dose réponse ; Rodentia ; Mammalia ; Vertebrata ; Toxicomanie ; Apprentissage ; Processus acquisition ;

Mots-clés espagnols / Spanish Keywords

Cocaína ; Estimulante SNC ; Psicotropo ; Sustancia toxicomanógena ; Droga ilícita ; Metabolito ; Toxicidad ; Locomoción ; Actividad física espontánea ; Reforzamiento ; Farmacocinética ; Plasma sanguíneo ; Sangre ; Relación farmacocinética farmacodinamia ; Condicionamiento instrumental ; Animal ; Rata ; Vía intravenosa ; Vía oral ; Ester ; Relación dosis respuesta ; Rodentia ; Mammalia ; Vertebrata ; Toxicomanía ; Aprendizaje ; Proceso adquisición ;

Localisation / Location

INIST-CNRS, Cote INIST : 1761, 35400009485476.0090