Catechol-o-methyltransferase inhibitor tolcapone improves learning and memory in naïve but not in haloperidol challenged rats

Document Type : Original Article

Authors

1 Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University Plovdiv, 15A Vassil Aprilov Blvd., Plovdiv 4002, Bulgaria

2 Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Medical University Plovdiv, 15A Vassil Aprilov Blvd., Plovdiv 4002, Bulgaria

Abstract

Objective(s): Dopamine plays an important role in cognitive functions. Inhibition of the dopamine-degrading enzyme catechol-O-methyltransferase (COMT) may have beneficial effects. Our aim was to assess the effect of COMT inhibitor tolcapone (TCP) on learning and memory in naïve and haloperidol-challenged rats.
Materials and Methods: Male Wistar rats were divided into 9 groups (n=8):  naïve-saline, tolcapone 5; 15 and 30 mg/kg BW; haloperidol (HP) challenged-saline, haloperidol, haloperidol+tolcapone 5; 15 and 30 mg/kg BW. Two-way active avoidance test (TWAA), elevated T-maze, and activity cage were performed. Observed parameters were: number of conditioned responses (CR) and unconditioned responses (UCR), working memory index, and vertical and horizontal movements.
Results: Naïve rats with 30 mg/kg BW TCP had a significantly increased number of CR  and  UCR during the long-term memory test. The animals with 5 mg/kg BW TCP significantly increased the number of UCR during the two retention tests. In haloperidol-challenged rats, the three experimental groups decreased the number of CR and UCR during the learning session and the two memory tests, compared to the saline group.  There was no significant difference between the HP-challenged rats treated with TCP and the haloperidol control group. All experimental naïve groups had significantly increased working memory index whereas none of the HP-challenged groups showed significant increase in this parameter.
Conclusion: Our results demonstrate that in naïve rats tolcapone improves memory in the hippocampal-dependent TWAA task and spatial working memory in T-maze.

Keywords

Main Subjects


1. Yang Y, Tang B, Guo JF. Parkinson’s disease and cognitive impairment. Parkinsons Dis 2016;2016:6734678.
2. Mosley RL, Benner EJ, Kadiu I, Thomas M, Boska MD, Hasan K, et al. Neuroinflamation, oxidative stress, and the pathogenesis of Parkinson’s disease. Clin Neurosci Res 2006; 6:261-281.
3. Chaudhuri KR1, Healy DG, Schapira AH. Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol 2006; 5:235-245.
4. Olanow CW, Tatton WG. Etiology and pathogenesis of Parkinson’s disease. Annu Rev Neurosci 1999; 22:123-144.
5. Wang YQ, Tang BS, Yan XX, Chen ZH, Xu Q, Liu ZH, et al. A neurospychological profile in Parkinson’s disease with mild cognitive impairment and dementia in China. J Clin Neurosci 2015; 22:981-985.
6. Solari N, Bonito-Oliva , Fisone G, Brambilla R. Understanding cognitive deficits in Parkinson’s disease: lessons from preclinical animal models. Learn Mem 2013; 20:592-600.
7. Ray NJ, Strafella AP. The neurobiology and neural circuitry of cognitive changes in Parkinson’s disease revealed by functional neuroimaging. Mov Disord 2012; 27:1484-1492.
8. Castro-Hernández J, Adlard PA, Finkelstein DI. Pramipexole restores depressed transmission in the ventral hippocampus following-MPTP-lesion. Sci Rep 2017; 7:44426
9. Calabresi P, Castrioto A, Di Filippo M, Picconi B Calabresi P, Castrioto A, et al. New experimental and clinical links between the hippocampus and the dopaminergic system in Parkinson’s disease. Lancet Neurol 2013; 12:811-821.
10. Mier D, Kirsch P, Meyer-Lindenberg A. Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis. Mol Psychiatry 2010; 15:918-27.
11. Käenmäki M, Tammimäki A, Myöhänen T, Pakarinen K, Amberg C, Karayiorgou M, et al. Quantitative role of COMT in dopamine clearance in the prefrontal cortex of freely moving mice. J Neurochem 2010;114:1745-55.
12. Witte AV, Flöel A. Effects of COMT polymorphisms on brain function and behavior in health and disease. Brain Res Bull 2012; 88:418-28.
13. Gasparini M, Fabrizio E, Bonifati V, Meco G. Cognitive improvement during Tolcapone treatment in Parkinson’s disease. J Neural Transm (Vienna) 1997; 104:887-894.
14. Apud JA, Mattay V, Chen J, Kolachana BS, Callicott JH, Rasetti R, et al. Tolcapone improves cognition and cortical information processing in normal human subjects. Neuropsychopharmacology 2007; 32:1011-1020.
15. Tunbridge EM, Bannerman DM, Sharp T, Harrison PJ. Catechol-O-methyltransferase inhibition improves set-shifting performance and elevated stimulated dopamine release in the rat prefrontal cortex. J Neurosci 2004; 24:5331-5335.
16. Laatikainen LM, Sharp T, Bannerman DM, PJ Harrison, Tunbridge EM. Modulation of hippocampla dopamine metabolism and hippocampal-dependent cognitive function by catechol-O-methyltransferase inhibition. J Psychopharmacol 2012; 26:1561–1568
17. Wang J, Bast T, Wang YC, Zhang WN. Hyppocampus and two-way active avoidance conditioniong : contrasting effects of cytotoxic lesion and temporary activation. Hippocampus 2015; 25:1517-1531.
18. Kulkarni SK, Bishoni M, Chopra K. In vivo microdialysis studies of strial level of neurotransmitters after haloperidol and chlorpromazine administration. Indian J Exp Biol 2009; 47:91-97.
19. Fanselow MS1, Dong HW. Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 2010; 65:7-19.
20. Mavanji V, Butterick TA, Duffy CM, Nixon JP, Billington CJ, Kotz CM. Orexin/hypocretin treatment restores hippocampal-dependent memory in orexin-deficient mice. Neurobiol Learn Mem 2017; 146:21-30.
21. Edelmann E, Lessmann V. Dopaminergic innervation and modulation of hippocampal networks. Cell Tissue Res 2018; 373:711-727.
22. Wei X, Ma T, Cheng Y, Huang CCY, Wang X, Lu J, et al. Dopamine D1 or D2 receptor-expressing neurons in the central nervous system. Addict Biol 2018; 23:569-584.
23. Hansen N, Manahan-Vaughan D. Dopamine D1/D5 receptors mediate informational saliency that promotes persistent hippocampal long-term plasticity. Cereb Cortex 2014; 24:845-58.
24. Rocchetti J, Isingrini E, Dal Bo G, Sagheby S, Menegaux A, Tronche F, et al. Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus. Biol Psychiatry 2015; 77:513-525.
25. Khromova I, Voronina T, Kraineva VA, Zolotov N, Männistö PT. Effects of selective catechol-O-methyltransferase inhibitors on single-trial passive avoidance retention in male rats. Behav Brain Res 1997; 86:49-57.
26. Matsumoto M, Weickert CS, Akil M, Lipska BK, Hyde TM, Herman MM, et al. Catechol O-methyltransferase mRNA expression in human and rat brain: evidence for a role in cortical neuronal function. Neuroscience 2003; 116:127-37.
27. Saavedra JM, Brownstein MJ, Palkovits M. Distribution of catechol-O-methyltransferase, histamine N-methyltransferase and monoamine oxidase in specific areas of the rat brain. Brain Res 1976; 118:152-156.
28. Kaakkola S, Gordin A, Männistö PT. General properties and clinical possibilities of new selective inhibitors of catechol O-methyltransferase. Gen Pharmacol 1994; 25:813-824.
29. Acquas E, Carboni E, de Ree RH, Da Prada M, Di Chiara G. Extracellular concentrations of dopamine and metabolites in the rat caudate after oral administration of a novel catechol-O-methyltransferase inhibitor Ro 40-7592. J Neurochem 1992; 59:326-30.
30. Borodovitsyna O, Flamini M, Chandler D. Noradrenergic Modulation of Cognition in Health and Disease. Neural Plast 2017; 2017:6031478.
31. Hashimoto T, Baba S, Ikeda H, Oda Y, Hashimoto K, Shimizu I. Lack of dopamine supersensitivity in rats after chronic administration of blonanserin: Comparison with haloperidol. Eur J Pharmacol 2018; 830:26-32.
32. Robbins TW, Arnsten AF. The neuropsychopharmacology of fronto-executive function: monoaminergic modulation. Annu Rev Neurosci 2009; 32:267-87.
33. Yang ST, Shi Y, Wang Q, Peng JY, Li BM. Neuronal representation of working memory in the medial prefrontal cortex of rats. Mol Brain 2014; 7:61.
34. Yang Y, Mailman RB. Strategic neuronal encoding in medial prefrontal cortex of spatial working memory in the T-maze. Behav Brain Res 2018; 343:50-60.
35. Lapish CC, Ahn S, Evangelista LM, So K, Seamans JK, Phillips AG. Tolcapone enhances food-evoked dopamine efflux and executive memory processes mediated by the rat prefrontal cortex. Psychopharmacology (Berl) 2009; 202(1-3):521-530.
36. Detrait ER, Carr GV, Weinberger DR, Lamberty Y. Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice. Behav Pharmacol 2016; 27:415-421.
37. Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, et al. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet 2004; 75:807-821.
38. Huotari M, Gogos JA, Karayiorgou M, Koponen O, Forsberg M, Raasmaja A, et al. Brain catecholamine metabolism in catechol-O-methyltransferase (COMT)-deficient mice. Eur J Neurosci 2002; 15:246-256.
39. Bezu M, Maliković J, Kristofova M, Engidawork E, Höger H, Lubec G, et al. Spatial working memory in male rats: Pre-experience and task dependent roles of dopamine D1- and D2-like receptors. Front Behav Neurosci 2017; 11:196.
40. Arnsten AF. Catecholamine modulation of prefrontal cortical cognitive function. Trends Cogn Sci 1998; 2: 436–447.
41. Luciana M, Collins PF. Dopaminergic modulation of working memory for spatial but not object cues in normal humans. J Cogn Neurosci 1997; 9:330-347.