P.2.16 Altered expression of hippocampal mGLUR7 mRNA in a model of depression

Abstract

Method: 34 participants were randomised to receive a single oral dose of either 5mg aripiprazole (n = 12), 1mg risperidone (n = 11), or placebo (n = 11) following a double blind study design. Particpants were instructed in the the N-Back task of working memory to ensure they fully understood task. 3.5 hours after drug administration participants underwent functional magnetic resonance imaging whilst performing the N-back task. Initial analysis focused on the 2-back condition. Images were acquired on a Philips Achiva 3Telsa scanner. Imaging data were preprocessed and analysed using SPM5. Reaction time and errors of omission and commission were recorded but behavioural data from 3 subjects were lost due to technical breakdown. Behavioural data were analysed with SPSS. Results: The 2-back task resulted in expected activations in dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, frontal pole, anterior cingulate and parietal cortices, irrespective of treatment group. Increased activation of the DLPFC and parietal cortex was seen in the aripiprazole group as compared with the placebo group. This was associated with a significantly faster reaction time for correct responses than the placebo group. Similarly, compared to the risperidone group, aripiprazole increased activation of the DLPFC and also the superior and inferior parietal lobe and the anterior cingulate. There were no significant behavioural differences between the aripiprazole and risperidone groups in number of errors or reaction times. Risperidone resulted in an increased activation of the bilateral frontal pole region as compared with both the placebo and aripiprazole group. The risperidone group produced less commission errors as compared with the placebo group. Conclusion: Both drugs improved performance on the working memory task but in different ways. Aripiprazole speeded reaction times and enhanced activation in DLPFC compared to placebo and in more widespread areas of the working memory network than risperidone. However risperidone decreased errors of commission suggesting reduced impulsivity and this was associated with increased frontal pole activation. The contrasting effects of two drugs may reflect the partial D2 agonist effects of aripiprazole and the more potent actions of risperidone on the 5-HT2A receptor. However, contrasting actions at the D2 receptor in the striatum cannot be excluded although no fMRI differences were observed in this region.