Evaluation Effects of Verapamil as a Calcium Channel Blocker on Acquisition, Consolidation and Retrieval of Memory in Mice
Subject Areas : Journal of Chemical Health RisksNooshin Masoudian Masoudian 1 , Nahid Masoudian 2 , Ali Rashidy Pour 3 , Abbas Ali Vafaei 4 , Sasan Andalib 5 , Golnaz Vaseghi 6
1 - Neurology Ward, Department of Internal Medicine, Kosar Hospital, School of Medicine, Semn
2 - Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
3 - Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
4 - Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
5 - Neurosciences Research Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
6 - Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
Keywords:
Abstract :
   Many factors are involved in learning and memory processes including brain nuclei, neurotransmitter systems, and the activity of ion channels. Studies showed inconsistent effects of calcium channel blockers on learning process, especially memory consolidation; however, little is known about their effect on memory acquisition and retrieval. Accordingly, the present study aimed to determine the effects of verapamil calcium channel antagonist as a representative of the phenylalkylamine group on different stages of memory and learning processes including acquisition, consolidation and retrieval in mice. In this experimental study, 150 male albino mice with a mean weight of 30 g were used. The mice were trained in a passive avoidance-learning task (1 mA shock for 2 seconds for evaluation of memory acquisition and consolidation and 3 seconds for evaluation of memory retrieval). The effect of verapamil (1, 2.5, 5, 10, and 20 mg/kg) on memory consolidation and the most effective dose of consolidation phase on memory acquisition and retrieval was assessed. For the evaluation of memory consolidation, the animals received the drug intraperitoneally immediately after training, while for evaluation of memory acquisition and retrieval, the drug was injected one hour before training. Memory retrieval test was performed 48 hours after training (the length of time it took the animal to enter the dark part of the device). The results showed that verapamil injection exerted no effect on memory acquisition and consolidation; nevertheless, it was capable to disrupt memory retrieval in 10 and 20 mg doses. These results indicate that as a phenylalkylamine calcium channel antagonist, high doses of verapamil can impair memory.Â
- Mallmann R. T., Elgueta C., Sleman F., Castonguay J., WilmesT., Van Den MaagdenbergA., et al., 2013. Ablation of CaV2.1 voltage-gated Ca(2+) channels in mouse forebrain generates multiple cognitive impairments. PLoS One. 8(10), e78598.
- Giordano T. P., Tropea T. F., SatputeS. S., Sinnegger-Brauns M. J., Striessnig J., Kosofsky B. E., et al.,2010. Molecular switch from L-type Ca v 1.3 to Ca v 1.2 Ca2+ channel signaling underlies long-term psychostimulant-induced behavioral and molecular plasticity. J Neurosci. 30, 17051âââ17062.
- Gangarossa G., Laffray S,, Bourinet E., Valjent E., . 2014. T-type calcium channel Cav3.2 deficient mice show elevated anxiety, impaired memory and reduced sensitivity to psycho stimulants. Front Behav Neurosci .8, 92.
- Chen C. C., Shen J. W., Chung N. C., Min M. Y., Cheng S. J., Liu, I. Y., 2012. Retrieval of context-associated memory is dependent on the Ca (v) 3.2 T-type calcium channel. PLoS One 7: e29384.
- Cheong E., Shin, H. S., 2013. T-type Ca2+ channels in normal and abnormal brain functions. Physiol Rev. 93, 961âââ992.
- Platenik J., Kuramoto N., Yoneda Y., 2000. Molecular mechanisms associated with long-term consolidation of the NMDA signals. Life Sci J. 67, 3350-3354.
- Chmaeau P., Qin Y., Spijker S., Smit A.B., Joles M., 2007. Glucocorticoids specifically enhance L-type calcium amplitude and affect calcium channel expression in the mouse hippocampus. J Neurophysiol. 97(1), 5-14.
- Krst H., Nair S., Velzing E., Rumpff-van Essen L., Slagter E., Shinnick-Gallagher P., Joles M., 2002. Glucocorticoids alter calcium conductance's and calcium channel subunit expression in basolateral amygdala neurons. Eur J Neu.16, 1083-1089.
- Luine V., Martinez C., Villegas M., Magarinos A.M., McEwen B.S., 1994. Restraint stress reversibly enhances spatial memory performance. Physiol Behav. 59, 27-32.
- McGaugh J.L., 2004. The amygdalae modulate the consolidation of memories of emotionally experience. The Ann Rev Neu. 27, 1âââ28.
- Quartermain D., Garcia deSoria V., 2001.The effects of calcium channel antagonists on short- and long-term retention in mice using spontaneous alternation behavior. Neurobiol Learn Mem. 76(1), 117-24.
- Kandel E.R., Schwrt J.H., Jesseu T.M., 2000.Principles of neural science .4th ed. McGraw-Hill Co,1228-1234.
- Quartermain D., 2000,Chronic administration of the Ca2+ channel blocker amlodipine facilitates learning and memory in mice. Eur J Pharmacol. 399(1), 57-63.
- Barad M., Blouin A.M., Cain C.K., 2004. Like extinction, latent inhibition of conditioned fear in mice is blocked by systemic inhibition of L-type voltage-gated calcium channels. Learn Mem. 11(5), 536-9.
- Ahmadiasl N., Alipour Mohammad R., Andalib S., Ebrahimi H., 2008. Effect of ghee oil on blood fat profile and passive avoidance learning in male rats. Medical Journal of Tabriz University of Medical Sciences. 30(3): 7-10.
- Ayromlu H., Masoudian N., Ahmadi-Asl N., Habibi P., Masoudian N., Andalib S., Yazdani M., Akbari H. 2014 Evaluation of Chronic and Acute Effects of Gabapentin on Passive Avoidance Learning Process in Mice. J Chem Health Risk. 4(3): 33-40.
- Lashgari R., Motamedi F., Noorbakhsh S.M., Zahedi-Asl S., Komaki A., Shahidi S., Haghparast A., 2007.Assessing the long-term role of L-type voltage dependent calcium channel blocker verapamil on short-term presynaptic plasticity at dentate gyrus of hippocampus. Neu Let. 415(2), 174-8.
- VanZwieten P.A., Pfaffendorf M., 1993. Pharmacology of the dihydropyridine calcium antagonists: relationship between lipophilicity and pharmacodynamic responses. J Hypertens Suppl. 11(6), S3-8.
- Auguet M., Clostre F., DeFeudis F.V., 1986. Effects of antidepressants on receptor-activated and Ca2+ activated contractions of rabbit isolated aorta. Gen Pharmacol. 17(5), 607-10.
- Quartermain D., DeSoria V.G., Kwan A., 2001. Calcium channel antagonists enhance retention of passive avoidance and maze learning in mice. Neurobiology of Learning and Memory. 75(1), 77-90.
- Weisskopf M.G., Bauer E.P., LeDoux J.E. ,1999. L-Type voltage-gated calcium channels mediate NMDA-independent associative long-term potentiation at thalamic input synapses to the amygdala. J Neu. 19,10512-10519.
- Seoane A., Massey P.V., Keen H., Bashir Z.I., Brown M.W. ,2009.L-type voltage-dependent calcium channel antagonists impair perirhinal long-term recognition memory and plasticity processes. J Neu. 29(30), 9534-44.
- Borroni A.M., Fichtenholtz H., Woodside B.L., Teyler T.J., 2000. Roll of voltage-dependent calcium channel Long Term Potentiation (LTP) and NMDA LT in spatial memory. J Neu. 20(24), 9272-9276.
- Rashidy-Pour A., Vafaei A.A., Taherian A.A., Miladi-Gorji H., Sadeghi H., Fathollahi Y., Bandehgi A.R., 2009. Verapamil enhances acute stress or glucocorticoid-induced deficits in retrieval of long-term memory in rats, Behav Brain Res.203, 76-80.