Effects of serotonin (5-HT)6 receptor ligands on responding for cocaine reward and seeking in rats.
Pharmacol Rep
; 62(6): 1005-14, 2010.
Article
em En
| MEDLINE
| ID: mdl-21273657
ABSTRACT
The endogenous brain serotonin (5-HT) system is believed to have an important modulatory influence in mediating drug reward and seeking mechanisms. Data from preclinical behavioral studies have provided emerging evidence that 5-HT(6) receptors, among other 5-HT receptors, may play a significant role in the mechanisms of action of psychostimulant addicted drugs. The aim of the present study was to investigate whether the selective pharmacological blockade or activation of 5-HT(6) receptors altered the maintenance of cocaine self-administration, reinstatement of cocaine-seeking behavior following an extinction of cocaine self-administration or cocaine-evoked conditioned place preference in rats. We also evaluated the effects of 5-chloro-N-(4-methoxy-3-piperazin-1-ylphenyl)-3-methyl)-2-benzothiophene-sulfonamide (SB 271046, a 5-HT(6) receptor antagonist) or N-1-(6-chloroimidazo-[2,1-b]-[1,3]thiazole-5-sulfonyl)tryptamine (WAY 181187, a potent 5-HT(6) receptor agonist) on locomotor activity in rats. Our results indicate that SB 271046 (1-10 mg/kg) altered cocaine-maintained self-administration as well as cocaine-evoked reinstatement of cocaine seeking and expression of cocaine place preference in rats.We also demonstrate that pharmacological stimulation of 5-HT(6) receptors by WAY 181187 (3-30 mg/kg) attenuated the expression of cocaine conditioned place preference but not cocaine self-administration and reinstatement of cocaine seeking. WAY 181187 at the highest dose used (30 mg/kg) reduced basal locomotor activity. Despite current results, the precise function and therapeutic relevance of 5-HT(6) receptors need further clarification.
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Base de dados:
MEDLINE
Assunto principal:
Recompensa
/
Antagonistas da Serotonina
/
Sulfonamidas
/
Tiazóis
/
Tiofenos
/
Triptaminas
/
Receptores de Serotonina
/
Agonistas do Receptor de Serotonina
/
Cocaína
/
Transtornos Relacionados ao Uso de Cocaína
Limite:
Animals
Idioma:
En
Revista:
Pharmacol Rep
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Polônia