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Background: Neuropeptides play an important role in various neural pathways, being able to control a wide spectrum of physiological responses. Neuropeptide Y (NPY) and proopiomelanocortin (POMC) functions are quite well studied, however little is known about their action at the level of limbic structures. The present work was focused on the expression of the aforementioned peptides in this brain structure of rats treated with olanzapine, a second generation neuroleptic drug. The detailed purpose of this experiment was the evaluation of potential relationships between chronic olanzapine administration and NPY and POMC mRNA expression in the amygdala and hippocampal formation., Methods: The studies were carried out on adult, male Sprague-Dawley rats that were divided into 2 groups: control and experimental animals treated with olanzapine (28 day-long intraperitoneal injection). All individuals were sacrificed under anaesthesia, then the amygdaloid complexes and hippocampi were excised. Total mRNA was isolated from homogenized samples of both structures and the RT-PCR method was used for estimation of NPY and POMC gene relative expression., Results: Prolonged olanzapine administration is reflected in qualitatively different changes in expression of NPY and POMC mRNA in the rat amygdala and hippocampus. Interestingly enough, olanzapine did not affect NPY expression, but significantly increased the POMC level in both examined regions., Conclusions: Olanzapine can affect amygdalar and hippocampal neuronal populations by the modulation of neuropeptide activity. Importantly, it may suggest the existence of an alternative mode of its action. Undoubtedly this hypothetic regulatory mechanism requires further pharmacological and neurostructural study., (Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)