Pharmacologia2044-46482044-4656Science International10.3923/pharmacologia.2015.258.263GeorgievaVerginia TashevRoman BelchevaStiliana 6201566Background and Objective: H1 receptor blockers, also called antihistamines inhibit the histamine receptors and terminate the effect of the released histamine. They are divided into three generations, according to the time of their synthesis, properties and side effects for therapeutic purposes. The objective of this research was to investigate the effects of antihistamines chlorpheniramine (1st generation), Loratadine (2nd generation) and Levocetirizine (3rd generation) applied i.p. and i.c.v. on learning and memory in male Wistar rats. Materials and Methods: A passive avoidance task (step through) was used as a test for learning and memory. Results: Chlorpheniramine (1st generation) applied i.p., at doses of 10 and 20 mg kg-1 impaired learning and memory processes expressed by the shortened latency time on the retention tests (3 and 24 h after training) and by the decreased percentage of rats that have reached the learning criterion while Loratadine (2nd generation) and Levocetirizine (3rd generation) at doses of 10 and 20 mg kg-1 did not affect significantly the performance of rats. The i.c.v. infusion of Chlorpheniramine, Loratadine and Levocetirizine at doses of 10 and 20 μg significantly impaired learning and memory. Comparing the effects of antihistamines after i.p and i.c.v. administration on the step through active avoidance response, it was found that Chlorpheniramine (1st generation) caused a potent inhibition of the avoidance response after its i.p and i.c.v. administration while Loratadine (2nd generation) and Levocetirizine (3rd generation) impaired learning and memory only after i.c.v. application. Conclusion: These findings suggest that the impaired learning and memory effect of antihistamines might be connected with inhibition of brain H1 receptors.]]>Moya‐Garcia, A.A., M.A. Medina and F. Sanchez‐Jimenez,2005275763Haas, H.L., O.A. Sergeeva and O. Selbach,20088811831241Brown, R.E., D.R. Stevens and H.L. Hass,200163637672Haas, H. and P. Panula,20034121130Kohler, C.A., W.C. da Silva, F. Benetti and J.S. Bonini,20112011Parsons, M.E. and C.R. Ganellin,2006147S127S135Unno, K., T. Ozaki, S. Mohammad, S. Tsuno, M. Ikeda-Sagara, K. Honda and M. Ikeda,2012683179185Katzung, B.G.,20039th Edn.,pp: 263-268pp: 263-268Yokoyama, H., M. Sato, K. Onodera and T. Watanabe,1996217194196Kamei, C., M. Ohuchi, Y. Sugimoto and C. Okuma,2000887183186Leurs, R., M.K. Church and M. Taglialatela,20021-antihistamines: Inverse agonism, anti-inflammatory actions and cardiac effects.]]>32489498Simons, F.E.R. and K.J. Simons,199433016631670Nolen, T.M.,1997193955Masuoka, T., A. Mikami, M. Yasuda, K. Shinomiya and C. Kamei,20071 receptor antagonists on hippocampal theta rhythm during spatial memory performance in rats.]]>5767782Chen, C., E. Hanson, J.W. Watson and J.S. Lee,200331312318Hair, P.I. and L.J. Scott,200666973996Kaliner, M.A., J. Oppenheimer and J.R. Farrar,201031112119Gupta, A., M. Gillard, B. Christophe, P. Chatelain, R. Massingham and M. Hammarlund‐Udenaes,20071 histamine receptor occupancy by levocetirizine, a non-sedating antihistamine; a time course study in the guinea pig.]]>15111291136Mimura, N., Y. Nagata, T. Kuwabara, N. Kubo and E. Fuse,200723106114Nonaka, A., F. Masuda, H. Nomura and N. Matsuki,201314931926Pellegrino, L. and A. Cushman,1967Buresova, O. and J. Bures,19832nd Edn.,pр: 135-208pр: 135-208Theunissen, E.L., A. Vermeeren, A.C.M. Van Oers, I. Van Maris and J.G. Ramaekers,200434250258Theunissen, E.L., A. Vermeeren, E.F. Vuurman and J.G. Ramaekers,20061225012509Vyas, B.M., A.J. Singh, A.S. Dhattiwala, S.M. Mansuri and V.J. Patel,2014537903795Hindmarch, I. and Z. Shamsi,199929133142Simons, F.E.R.,200435122032217Timmerman, H.,200055510Onodera, K., A. Yamatodani, T. Watanabe and H. Wadas,199442685702Kamei, C., Y. Okumura and K. Tasaka,1993111376382Kamei, C., Y.H. Chung and K. Tasaka,19901-blockers on the step-through active avoidance response in rats.]]>102312318Kamei, C. and K. Tasaka,19911-blockers.]]>57473482Montoro, J., J. Sastre, J. Bartra, A. Del Cuvillo and I. Davila et al.,2006162428Van Ruitenbeek, P., A. Vermeeren and W.J. Riedel,20101 receptor antagonist cetirizine impairs working memory processing speed, but not episodic memory.]]>161456466