Neurotensin Receptor 1 Gene (NTSR1) Polymorphism Is Associated with Working Memory

BACKGROUND: Recent molecular genetics studies showed significant associations between dopamine-related genes (including genes for dopamine receptors, transporters, and degradation) and working memory, but little is known about the role of genes for dopamine modulation, such as those related to neurotensin (NT), in working memory. A recent animal study has suggested that NT antagonist administration impaired working memory in a learning task. The current study examined associations between NT genes and working memory among humans. METHODS: Four hundred and sixty healthy undergraduate students were assessed with a 2-back working memory paradigm. 5 SNPs in the NTSR1 gene were genotyped. 5 ANOVA tests were conducted to examine whether and how working memory differed by NTSR1 genotype, with each SNP variant as the independent variable and the average accuracy on the working memory task as the dependent variable. RESULTS: ANOVA results suggested that two SNPs in the NTSR1 gene (rs4334545 and rs6090453) were significantly associated with working memory. These results survived corrections for multiple comparisons. CONCLUSIONS: Our results demonstrated that NTSR1 SNP polymorphisms were significantly associated with variance in working memory performance among healthy adults. This result extended previous rodent studies showing that the NT deficiency impairs the working memory function. Future research should replicate our findings and extend to an examination of other dopamine modulators

: Neurotensin and cocaine sensitization

International audienceChronic use of psychostimulants induces enduringly increased responsiveness to a subsequent psychostimulant injection and sensitivity to drug-associated cues, contributing to drug craving and relapse. Neurotensin (NT), a neuropeptide functionally linked to dopaminergic neurons, was suggested to participate in these phenomena. We and others have reported that SR 48692, an NT receptor antagonist, given in pre- or co-treatments with cocaine or amphetamine, alters some behavioral effects of these drugs in rats. However, its efficacy when applied following repeated cocaine administration remains unknown. We, therefore, evaluated the ability of SR 48692, administered after a cocaine regimen, to interfere with the expression of locomotor sensitization and conditioned place preference (CPP) in rats. We demonstrated that the expression of locomotor sensitization, induced by four cocaine injections (15 mg/kg, i.p.) every other day and a cocaine challenge 1 week later, was attenuated by a subsequent 2-week daily administration of SR 48692 (1 mg/kg, i.p.). Furthermore, the expression of cocaine-induced CPP was suppressed by a 10-day SR 48692 treatment started after the conditioning period (four 15 mg/kg cocaine injections every other day). Taken together, our data show that a chronic SR 48692 treatment given after a cocaine regimen partly reverses the expression of locomotor sensitization and CPP in the rat, suggesting that NT participates in the maintenance of these behaviors. Our results support the hypothesis that targeting neuromodulatory systems, such as the NT systems may offer new strategies in the treatment of drug addiction