P.1.003 Brain-derived neurotrophic factor as a biomarker of clinical response in bipolar disorder: 16-week follow-up study

Abstract

Simultaneous infusion of the selective 5-HT2A-receptor antagonist M100907, as well as asenapine, completely blocked the DOI-induced increase in dopamine and serotonin release and partially the increased noradrenaline release, indicating a similar mechanism by M100907 and asenapine. When given alone, infusion of M100907 or asenapine, in the concentrations used, did not affect monoamine release. Intracortical administration of the selective a2adrenoceptor agonist clonidine significantly decreased dopamine, noradrenaline and serotonin release in the mPFC (maximal effects; 61.0±8.0, 50.4±7.6, and 67.0±4.1% of baseline, respectively; p< 0.01–0.001). Simultaneous infusion of the a2-adrenoceptor antagonist idazoxan blocked the clonidine-induced reduction of dopamine and noradrenaline release. The effect of idazoxan on serotonin was less pronounced and not statistically significant. Simultaneous infusion of asenapine did not acutely block the clonidine-induced decrease in transmitter release. However, following termination of the clonidine infusion the transmitter release remained at a low level. During this interval, i.e. the following hour after the clonidine infusion, intracortical infusion of asenapine restored the catecholamine release to baseline level, indicating an a2-adrenoceptor blocking effect of asenapine which was somewhat delayed. When given alone, the infusion of idazoxan or asenapine, in the concentrations used, did not affect monoamine release. Our results propose that local application of asenapine in the mPFC indeed exhibits a pharmacological significant 5-HT2Aand, to a weaker extent, a2-receptor antagonistic activity. Whereas its 5-HT2A blocking property preferentially influenced the release of serotonin and dopamine but only to a lesser extent noradrenaline, blockage of a2-adrenoceptors preferentially influenced dopamine and noradrenaline release, albeit the effect was somewhat delayed. Thus, 5-HT2A-receptor antagonism and a2-adrenoceptor blockage induced by asenapine in the mPFC may contribute to enhance prefrontal monoamine release in vivo and, secondarily, its effect on positive and negative symptoms as well as pro-cognitive and antidepressant effects [1,2].