The evaluation between histaminergic and cholinergic neurotransmission on object recognition and emotional memory

Abstract

Several authors have been investigated and demonstrated that the histaminergic system of the central nervous system influences directly or indirectly (through interaction with other neurotransmitters) mnemonic process. One of these interactions occurs with acetylcholine, and there is clear evidence indicating that histamine controls the release of central acetylcholine locally in the cortex and amygdala, and activating cholinergic neurons in the nucleus basalis magnocellularis and the medial septal area-diagonal band that project to the cortex and to the hippocampus, respectively. The blockade of H3 autoreceptors augmented histamine release within the nucleus basalis magnocellularis, and that histamine in turn activates postsynaptic H2 receptors responsible for the potentiated expression of fear response or postsynaptic H1 receptors responsible for the improvement in the object recognition task. However, it is still unknown the hole of histaminergic H1 agonists for their ability to: modulate acetylcholine release from discrete brain regions which are known to be necessary for expressing specific behaviors (namely, prefrontal cortex and amygdala); affect the behavioral responses in a task dependent mainly on the cortical cholinergic system (object recognition), and in a second task mainly dependent on the cholinergic system in the amygdala (contextual fear conditioning). Therefore, the aim of this study is investigate the ability of histaminergic H1 agonists to modulate acetylcholine release from the basolateral amygdala, and the prefrontal cortex. The modulation of acetylcholine will be evaluated with microdialysis. Acetylcholine extracellular levels will be measured by HPLC-electrochemical detection. The behavioral analysis will be evaluated on object recognition and on contextual fear conditioning. (AU)