Cocaine-like discriminative stimulus effects of "norepinephrine-preferring" monoamine releasers: time course and interaction studies in rhesus monkeys.
Psychopharmacology (Berl)
; 234(23-24): 3455-3465, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-28889212
ABSTRACT
RATIONALE The therapeutic potential of monoamine releasers with prominent dopaminergic effects is hindered by their high abuse liability. OBJECTIVES:
The present study examined the effects of several novel "norepinephrine (NE)-preferring" monoamine releasers relative to non-selective monoamine releasers, d-amphetamine and d-methamphetamine, in rhesus monkeys trained to discriminate cocaine. NE-preferring releasers were approximately 13-fold more potent for NE compared to dopamine release and ranged in potency for serotonin release (PAL-329 < l-methamphetamine < PAL-169).METHODS:
Adult rhesus macaques were trained to discriminate 0.4 mg/kg, IM cocaine on a 30-response fixed ratio schedule of food reinforcement. Substitution studies determined the extent to which test drugs produced cocaine-like discriminative stimulus effects and their time course. Drug interaction studies determined whether pretreatment with test drugs altered the discriminable effects of cocaine.RESULTS:
Results show that cocaine, d-amphetamine, and d-methamphetamine dose-dependently substituted for cocaine with similar potencies. Among the "NE-preferring" releasers, PAL-329 and l-methamphetamine also dose-dependently substituted for cocaine but differed in potency. PAL-169 failed to substitute for cocaine up to a dose that disrupted responding. When administered prior to cocaine, only d-amphetamine and PAL-329 significantly shifted the cocaine dose-effect function leftward indicating enhancement of cocaine's discriminative stimulus effects.CONCLUSIONS:
These data suggest that greater potency for NE relative to dopamine release (up to 13-fold) does not interfere with the ability of a monoamine releaser to produce cocaine-like discriminative effects but that increased serotonin release may have an inhibitory effect. Further characterization of these and other "NE-preferring" monoamine releasers should provide insight into their potential for the management of cocaine addiction.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cocaína
/
Aprendizagem por Discriminação
/
Proteínas da Membrana Plasmática de Transporte de Dopamina
/
Proteínas da Membrana Plasmática de Transporte de Norepinefrina
/
Proteínas da Membrana Plasmática de Transporte de Serotonina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Psychopharmacology (Berl)
Ano de publicação:
2017
Tipo de documento:
Article