REV.CHIM.(Bucharest)♦69♦No.12♦2018 http://www.revistadechimie.ro The Imidazoline Receptor Antagonists Idazoxan and Efaroxan Improve the Spatial and Reference Memory in Rats GABRIELA RUSU-ZOTA 1 , ANDREI LUCA 2,3 *, GABRIELA DUMITRITA STANCIU 3 , VICTORITA SORODOC 4 , MARIA MAGDALENA LEON-CONSTANTIN 5 , BOGDAN STOICA 6 , CRISTINA GALES 7 , TEODORA ALEXA-STRATULAT 8 1 Grigore T. Popa University of Medicine and Pharmacy, Department of Pharmacology, Clinical Pharmacology and Algesiology, 16 Universitatii Str., 700115, Iasi, Romania 2 Grigore T. Popa University of Medicine and Pharmacy, Department of Pneumology,16 Universitatii Str., 700115, Iasi, Romania 3 Center for Advanced Research and Development in Experimental Medicine (CEMEX), Str9-13 M. Kogalniceanu Str., 700454, Iasi, Romania 4 Grigore T. Popa University of Medicine and Pharmacy, Department of Internal Medicine, 16 Universitatii Str., 700115, Iasi, Romania 5 Grigore T. Popa University of Medicine and Pharmacy, Department of Medical Semiology, 16 Universitatii Str., 700115, Iasi, Romania 6 Grigore T. Popa University of Medicine and Pharmacy, Faculty of Medicine, Department of Biochemistry, 16 Universitatii Str., 700115, Iasi, Romania 7 Grigore T. Popa University of Medicine and Pharmacy, Department of Histology , 16 Universitatii Str., 700115, Iasi, Romania 8 Grigore T. Popa University of Medicine and Pharmacy, Department of Medical Oncology-Radiotherapy , 16 Universitatii Str., 700115, Iasi, Romania Experimental studies and clinical trials revealed the complex interconnections between imidazoline system and various other mediators such as epinephrine, norepinephrine; thus, explain their involvement in the pathophysiological mechanisms of different motor, behavioral and cognitive disturbances. In this study, we tested the influence induced by idazoxan and efaroxan on the cognitive performances in rats. Groups of 6 adult male Wistar rats were treated intraperitoneally according to the following protocol: group I (Control): distilled water 0.3 ml/100g; group II (IDZ): 3 mg/kg idazoxan and group III (EFR): 1 mg/kg efaroxan. The effects of the imidazoline receptor antagonists on the rats cognitive functions were assessed using the radial-arm maze, in order to count the time spent into the arms, the number of baited arms visited, but previously explored (working memory errors); the time taken to consume all baits and the number of entering in non-baited arms (reference memory errors). The data were expressed as mean + /- standard deviation, and statistically analyzed using SPSS version 17.0 Software for Windows, followed by ANOVA one-way method. The administration of IDZ, as well as of EFR was accompanied by a substantial diminution in the number of working memory errors, and the period of time to consume all baits, statistically significant (p< 0.01) compared to control group. The use of these two imidazoline receptors antagonists resulted in a considerable decrease in the reference memory errors number, statistically significant (p< 0.01) compared to the group treated with distilled water. The influence of IDZ on the evaluated parameters was more accentuated than the effects induced by EFR in all sessions of testing, in this behavioral experimental model. Our findings indicate that treatment with both imidazoline receptor antagonists, idazoxan and efaroxan was associated by a facilitation of the short-term memory retention, an enhancement of discriminative spatial learning, and an improvement of long-term memory performance in radial arm maze in rats. Keywords: imidazoline receptors antagonists, spatial and reference memory, rats *e-mail lc_andrei@yahoo.com Phone: + 40(757762607) All authors contributed equally to this paper Imidazoline is a class of heterocycles formally derived from imidazole’s by the reduction of one of the two double bonds. Three isomers are known, 2-imidazolines, 3- imidazolines, and 4-imidazolines. The 2- and 3-imidazolines contain an imine center, whereas the 4-imidazolines contain an alkene group [1]. Discovered in 1984, imidazoline receptors (I1 receptor appears to be a G protein- coupled receptor involved in inhibition of the sympathetic nervous system to lower blood pressure; I2 receptor modulate the level of central monoamines, with potential antidepressant and antinociceptive activity and I3, regulates insulin secretion from pancreatic beta cells) are both central and peripheral, influencing several physiological and pathological processes [1]. Imidazoline system is one of the major structures involved in the functioning of the human body: inhibitory sympathetic action; neuroprotective effects and mediation of the nociceptive sensitivity, insulinotropic activity, mediation of the addictive phenomenon and antidepressant activity [2]. Literature data have revealed the implication of imidazoline receptors in some pathophysiological (regulation of adipose tissue formation, feeding behavior) and pathological pathways involved in epilepsy and processes of neoplastic cell transformation [3,4]. The potent neurotransmitter of imidazoline system, agmatine contributes in the mediation of the body’s response to stress, in analgesia, drug addiction, withdrawal syndrome and in neuroprotection [4-6]. Deepening investigations related to the participation of substances acting on the imidazoline receptors, on behavior, memory, locomotor activity, is a starting point for getting new information about the pathophysiological mechanisms of spontaneous behavior disturbances and 3577