P.2.021 Role of adenosine (A)2A receptor in nicotine addiction – pharmacological and genetic aspects

Abstract

Therefore, in order to identify the implication of 5-HT7R on the onset of the age-related memory decline, memory performances of 7−8 months-old and 10−12 months-old KO C57BL/6J mice with homozygous disruption of the 5-HT7R gene were compared to paired wild type mice (WT). Recognition memory performances were assessed in a Y-maze with a 1-hour delay between presentation and test [2]. Spatial working memory performances were assessed by recording spontaneous alternation behaviour in a Y-maze during a 5-minutes session. In addition locomotor activity was assessed in an activity cage and anxiety-related behaviour was examined using the elevated plus-maze (EPM). Our data showed that 10−12 months-old WT mice did not discriminate the novel object contrary to 7−8 monthsold WT mice, which spent more time exploring the novel object compared to the chance level (univariate t-test: p< 0.05). In addition, disruption of 5-HT7R led to an impaired object discrimination in 7−8 and 10−12 monthsold mice. By contrast, ANOVA analysis revealed that mutant mice exhibited equivalent levels of spontaneous alternation compared to WT mice (around 75%). In addition, statistical analysis of locomotor activity did not revealed any significant effect of genotype or genotype × age interaction, indicating equivalent basal level of locomotion. Finally, no differences between mice of both genotypes were detected in the global activity or the anxiety-related parameters assessed in the EPM. Our results therefore suggest that in our experimental conditions, the onset of episodic-like memory decline is situated between 7−8 and 10−12 months-old of age in C57BL/6J mice, and that the lack of 5-HT7R could accelerate the onset of this decline, with no relation to any inhibition of locomotor activity or increased anxiety-like behaviour. By contrast, working memory performances seem not to be affected between 7−8 and 10−12 monthsold in KO and WT mice. Further pharmacological (using a selective 5-HT7 antagonist) and molecular (5-HT7R expression) studies in WT mice would confirm this statement.