Working memory- and anxiety-related behavioral effects of repeated nicotine as a stressor: the role of cannabinoid receptors

BMC Neuroscience

Tamaki Hayase¹ 

[1] Department of Legal Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan

关键词: virodhamine;    CP 55,940;    AM 251;    Cannabinoid;    Anxiety;    Working memory;    Immobilization stress;    Nicotine;   

Others  :  1140448
DOI  :  10.1186/1471-2202-14-20

 received in 2012-07-14, accepted in 2013-01-31,  发布年份 2013

【 摘 要 】

Background

Like emotional symptoms such as anxiety, modulations in working memory are among the frequently-reported but controversial psychiatric symptoms associated with nicotine (NC) administration. In the present study, repeated NC-induced modulations in working memory, along with concurrently-observed anxiety-related behavioral alterations, were investigated in mice, and compared with the effects of a typical cognition-impairing stressor, immobilization stress (IM). Furthermore, considering the structural and functional contributions of brain cannabinoid (CB) receptors in NC-induced psychiatric symptoms including emotional symptoms, the interactive effects of brain CB receptor ligands (CB ligands) and NC and/or IM on the working memory- and anxiety-related behaviors were examined.

Results

Statistically significant working memory impairment-like behavioral alterations in the Y-maze test and anxiety-like behavioral alterations in the elevated plus-maze (EPM) test were observed in the groups of mice treated with 0.8 mg/kg NC (subcutaneous (s.c.) 0.8 mg/kg treatment, 4 days) and/or IM (10 min treatment, 4 days). In the group of mice treated with NC plus IM (NC-IM group), an enhancement of the behavioral alterations was observed. Among the CB type 1 (CB1) antagonist AM 251 (AM), the non-selective CB agonist CP 55,940 (CP), and the CB1 partial agonist/antagonist virodhamine (VD), significant recovering effects were provided by AM (0.2-2.5 mg/kg) and VD (5 mg/kg) against the working memory impairment-like behaviors, whereas significant anxiolytic-like effects (recoveries from both attenuated percentage of entries into open arms and attenuated percentage of time spent on open arms) were provided by VD (1–10 mg/kg) and CP (2 mg/kg) against the anxiety-like behaviors.

Conclusions

Although working memory impairment- and anxiety-like behavioral alterations were commonly induced in the NC, IM, and NC-IM groups and the therapeutic involvement of CB receptors was shown, there were discrepancies in the types of effective CB ligands between the working memory- and anxiety-related behaviors. The differential involvements of CB receptor subtypes and indirectly activated neurotransmitter systems may contribute to these discrepancies.

【 授权许可】

   
2013 Hayase; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Zarocostas J: WHO report warns deaths from tobacco could rise beyond eight million a year by 2030. BMJ 2008, 336:299.
• [2]WHO report on the global tobacco epidemic 2011. [http://www.who.int/tobacco/global_report/2011/en/ webcite]
• [3]Heishman SJ: Behavioral and cognitive effects of smoking: relationship to nicotine addiction. Nicotine Tob Res 1999, 1(Suppl 2):143-147.
• [4]Anstey KJ, von Sanden C, Salim A, O'Kearney R: Smoking as a risk factor for dementia and cognitive decline: a meta-analysis of prospective studies. Am J Epidemiol 2007, 166:367-378.
• [5]Llewellyn DJ, Lang IA, Langa KM, Naughton F, Matthews FE: Exposure to secondhand smoke and cognitive impairment in non-smokers: national cross sectional study with cotinine measurement. BMJ 2009, 338:b462.
• [6]Khan ZU, Muly EC: Molecular mechanisms of working memory. Behav Brain Res 2011, 219:329-341.
• [7]Xu J, Mendrek A, Cohen MS, Monterosso J, Rodriguez P, Simon SL, Brody A, Jarvik M, Domier CP, Olmstead R, Ernst M, London ED: Brain activity in cigarette smokers performing a working memory task: effect of smoking abstinence. Biol Psychiatry 2005, 58:143-150.
• [8]Malin DH, Goyarzu P: Rodent models of nicotine withdrawal syndrome. Handb Exp Pharmacol 2009, 192:401-434.
• [9]Park S, Knopick C, McGurk S, Meltzer HY: Nicotine impairs spatial working memory while leaving spatial attention intact. Neuropsychopharmacology 2000, 22:200-209.
• [10]Jacobsen LK, Krystal JH, Mencl WE, Westerveld M, Frost SJ, Pugh KR: Effects of smoking and smoking abstinence on cognition in adolescent tobacco smokers. Biol Psychiatry 2005, 57:56-66.
• [11]Swan GE, Lessov-Schlaggar CN: The effects of tobacco smoke and nicotine on cognition and the brain. Neuropsychol Rev 2007, 17:259-273.
• [12]Toledano A, Alvarez MI, Toledano-Díaz A: Diversity and variability of the effects of nicotine on different cortical regions of the brain - therapeutic and toxicological implications. Cent Nerv Syst Agents Med Chem 2010, 10:180-206.
• [13]Foulds J, Stapleton J, Swettenham J, Bell N, McSorley K, Russell MA: Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers. Psychopharmacology (Berl) 1996, 127:31-38.
• [14]Phillips S, Fox P: An investigation into the effects of nicotine gum on short-term memory. Psychopharmacology (Berl) 1998, 140:429-433.
• [15]Rezvani AH, Levin ED: Cognitive effects of nicotine. Biol Psychiatry 2001, 49:258-267.
• [16]Ernst M, Heishman SJ, Spurgeon L, London ED: Smoking history and nicotine effects on cognitive performance. Neuropsychopharmacology 2001, 25:313-319.
• [17]Kleykamp BA, Jennings JM, Blank MD, Eissenberg T: The effects of nicotine on attention and working memory in never-smokers. Psychol Addict Behav 2005, 19:433-438.
• [18]Balerio GN, Aso E, Maldonado R: Role of the cannabinoid system in the effects induced by nicotine on anxiety-like behaviour in mice. Psychopharmacology (Berl) 2006, 184:504-513.
• [19]Caldarone BJ, King SL, Picciotto MR: Sex differences in anxiety-like behavior and locomotor activity following chronic nicotine exposure in mice. Neurosci Lett 2008, 439:187-191.
• [20]Kupferschmidt DA, Funk D, Erb S, Lê AD: Age-related effects of acute nicotine on behavioural and neuronal measures of anxiety. Behav Brain Res 2010, 213:288-292.
• [21]Mizoguchi K, Yuzurihara M, Ishige A, Sasaki H, Chui DH, Tabira T: Chronic stress induces impairment of spatial working memory because of prefrontal dopaminergic dysfunction. J Neurosci 2000, 20:1568-1574.
• [22]Shansky RM, Rubinow K, Brennan A, Arnsten AF: The effects of sex and hormonal status on restraint-stress-induced working memory impairment. Behav Brain Funct 2006, 2:8. BioMed Central Full Text
• [23]Schoofs D, Preuss D, Wolf OT: Psychosocial stress induces working memory impairments in an n-back paradigm. Psychoneuroendocrinology 2008, 33:643-653.
• [24]MacNeil G, Sela Y, McIntosh J, Zacharko RM: Anxiogenic behavior in the light–dark paradigm follwoing intraventricular administration of cholecystokinin-8S, restraint stress, or uncontrollable footshock in the CD-1 mouse. Pharmacol Biochem Behav 1997, 58:737-746.
• [25]Chotiwat C, Harris RB: Increased anxiety-like behavior during the post-stress period in mice exposed to repeated restraint stress. Horm Behav 2006, 50:489-495.
• [26]Middleton LS, Cass WA, Dwoskin LP: Nicotinic receptor modulation of dopamine transporter function in rat striatum and medial prefrontal cortex. J Pharmacol Exp Ther 2004, 308:367-377.
• [27]Singer S, Rossi S, Verzosa S, Hashim A, Lonow R, Cooper T, Sershen H, Lajtha A: Nicotine-induced changes in neurotransmitter levels in brain areas associated with cognitive function. Neurochem Res 2004, 29:1779-1792.
• [28]Wall PM, Messier C: Concurrent modulation of anxiety and memory. Behav Brain Res 2000, 109:229-241.
• [29]Clinton SM, Sucharski IL, Finlay JM: Desipramine attenuates working memory impairments induced by partial loss of catecholamines in the rat medial prefrontal cortex. Psychopharmacology (Berl) 2006, 183:404-412.
• [30]Blanco E, Castilla-Ortega E, Miranda R, Begega A, Aguirre JA, Arias JL, Santín LJ: Effects of medial prefrontal cortex lesions on anxiety-like behaviour in restrained and non-restrained rats. Behav Brain Res 2009, 201:338-342.
• [31]Goldwater DS, Pavlides C, Hunter RG, Bloss EB, Hof PR, McEwen BS, Morrison JH: Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recovery. Neuroscience 2009, 164:798-808.
• [32]Parrott AC: Does cigarette smoking cause stress? Am Psychol 1999, 54:817-820.
• [33]Parrott AC, Kaye FJ: Daily uplifts, hassles, stresses and cognitive failures: in cigarette smokers, abstaining smokers, and non-smokers. Behav Pharmacol 1999, 10:639-646.
• [34]Kita T, Okamoto M, Kubo K, Tanaka T, Nakashima T: Enhancement of sensitization to nicotine-induced ambulatory stimulation by psychological stress in rats. Prog Neuropsychopharmacol Biol Psychiatry 1999, 23:893-903.
• [35]Lutfy K, Brown MC, Nerio N, Aimiuwu O, Tran B, Anghel A, Friedman TC: Repeated stress alters the ability of nicotine to activate the hypothalamic-pituitary-adrenal axis. J Neurochem 2006, 99:1321-1327.
• [36]Schiltz CA, Kelley AE, Landry CF: Acute stress and nicotine cues interact to unveil locomotor arousal and activity-dependent gene expression in the prefrontal cortex. Biol Psychiatry 2007, 61:127-135.
• [37]Childs E, de Wit H: Hormonal, cardiovascular, and subjective responses to acute stress in smokers. Psychopharmacology (Berl) 2009, 203:1-12.
• [38]Kotlyar M, Drone D, Thuras P, Hatsukami DK, Brauer L, Adson DE, al'Absi M: Effect of stress and bupropion on craving, withdrawal symptoms, and mood in smokers. Nicotine Tob Res 2011, 13:492-497.
• [39]Minowa K, Pawlak R, Takada Y, Takada A: Nicotine attenuates stress-induced changes in plasma amino acid concentrations and locomotor activity in rats. Brain Res Bull 2000, 51:83-88.
• [40]Hsu HR, Chen TY, Chan MH, Chen HH: Acute effects of nicotine on restraint stress-induced anxiety-like behavior, c-Fos expression, and corticosterone release in mice. Eur J Pharmacol 2007, 566:124-131.
• [41]Andreasen JT, Henningsen K, Bate S, Christiansen S, Wiborg O: Nicotine reverses anhedonic-like response and cognitive impairment in the rat chronic mild stress model of depression: comparison with sertraline. J Psychopharmacol 2011, 25:1134-1141.
• [42]Aleisa AM, Alzoubi KH, Gerges NZ, Alkadhi KA: Nicotine blocks stress-induced impairment of spatial memory and long-term potentiation of the hippocampal CA1 region. Int J Neuropsychopharmacol 2006, 9:417-426.
• [43]Hayase T: Chronologically overlapping occurrences of nicotine-induced anxiety- and depression-related behavioral symptoms: effects of anxiolytic and cannabinoid drugs. BMC Neurosci 2007, 8:76. BioMed Central Full Text
• [44]Hayase T: Depression-related anhedonic behaviors caused by immobilization stress: a comparison with nicotine-induced depression-like behavioral alterations and effects of nicotine and/or “antidepressant” drugs. J Toxicol Sci 2011, 36:31-41.
• [45]Riebe CJ, Wotjak CT: Endocannabinoids and stress. Stress 2011, 14:384-397.
• [46]Castañé A, Valjent E, Ledent C, Parmentier M, Maldonado R, Valverde O: Lack of CB1 cannabinoid receptors modifies nicotine behavioural responses, but not nicotine abstinence. Neuropharmacology 2002, 43:857-867.
• [47]Picciotto MR, Caldarone BJ, King SL, Zachariou V: Nicotinic receptors in the brain. Links between molecular biology and behavior. Neuropsychopharmacology 2000, 22:451-465.
• [48]Viveros MP, Marco EM, Llorente R, Lamota L: The role of the hippocampus in mediating emotional responses to nicotine and cannabinoids: a possible neural substrate for functional interactions. Behav Pharmacol 2007, 18:375-389.
• [49]Riedel G, Davies SN: Cannabinoid function in learning, memory and plasticity. Handb Exp Pharmacol 2005, 168:445-477.
• [50]Marsicano G, Lafenêtre P: Roles of the endocannabinoid system in learning and memory. Curr Top Behav Neurosci 2009, 1:201-230.
• [51]Biala G, Kruk M: Cannabinoid receptor ligands suppress memory-related effects of nicotine in the elevated plus maze test in mice. Behav Brain Res 2008, 192:198-202.
• [52]Mateos B, Borcel E, Loriga R, Luesu W, Bini V, Llorente R, Castelli MP, Viveros MP: Adolescent exposure to nicotine and/or the cannabinoid agonist CP 55,940 induces gender-dependent long-lasting memory impairments and changes in brain nicotinic and CB(1) cannabinoid receptors. J Psychopharmacol 2011, 25:1676-1690.
• [53]Viveros MP, Marco EM, File SE: Endocannabinoid system and stress and anxiety responses. Pharmacol Biochem Behav 2005, 81:331-342.
• [54]Moreira FA, Wotjak CT: Cannabinoids and anxiety. Curr Top Behav Neurosci 2010, 2:429-450.
• [55]Hayase T, Yamamoto Y, Yamamoto K: Stress-related behavioral alterations accompanying cocaine toxicity: the effects of mixed opioid drugs. Nihon Arukoru Yakubutsu Igakkai Zasshi 2000, 35:402-414.
• [56]Committee on Animal Research of Kyoto University Faculty of Medicine: Guidelines for Animal Experiments of Kyoto University Faculty of Medicine. [http://www.kyoto-u.ac.jp/uni_int/kitei/reiki_honbun/w002RG00001169.html webcite] (Japanese)
• [57]Armario A, Gil M, Marti J, Pol O, Balasch J: Influence of various acute stressors on the activity of adult male rats in a holeboard and in the forced swim test. Pharmacol Biochem Behav 1991, 39:373-377.
• [58]Hayase T: Memory-related and anxiogenic effects of nicotine: roles of cannabinoid receptors. Nihon Arukoru Yakubutsu Igakkai Zasshi 2009, 44:440-441. (Japanese)
• [59]Yoshida T, Sakane N, Umekawa T, Kondo M: Effect of nicotine on sympathetic nervous system activity of mice subjected to immobilization stress. Physiol Behav 1994, 55:53-57.
• [60]Sarter M, Bodewitz G, Stephens DN: Attenuation of scopolamine-induced impairment of spontaneous alteration behaviour by antagonist but not inverse agonist and agonist beta-carbolines. Psychopharmacology (Berl) 1988, 94:491-495.
• [61]Parada-Turska J, Turski WA: Excitatory amino acid antagonists and memory: effect of drugs acting at N-methyl-D-aspartate receptors in learning and memory tasks. Neuropharmacology 1990, 29:1111-1116.
• [62]Pellow S, Chopin P, File SE, Briley M: Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 1985, 14:149-167.
• [63]File SE, Aranko K: Sodium valproate and chlordiazepoxide in the elevated plus-maze test of anxiety in the rat. Neuropsychobiology 1988, 20:82-86.
• [64]Prior H, Schwegler H, Marashi V, Sachser N: Exploration, emotionality, and hippocampal mossy fibers in nonaggressive AB/Gat and congenic highly aggressive mice. Hippocampus 2004, 14:135-140.
• [65]Alves SH, Pinheiro G, Motta V, Landeira-Fernandez J, Cruz AP: Anxiogenic effects in the rat elevated plus-maze of 5-HT(2C) agonists into ventral but not dorsal hippocampus. Behav Pharmacol 2004, 15:37-43.
• [66]File SE, Kenny PJ, Cheeta S: The role of the dorsal hippocampal serotonergic and cholinergic systems in the modulation of anxiety. Pharmacol Biochem Behav 2000, 66:65-72.
• [67]Seth P, Cheeta S, Tucci S, File SE: Nicotinic–serotonergic interactions in brain and behaviour. Pharmacol Biochem Behav 2002, 71:795-805.
• [68]Hale MW, Shekhar A, Lowry CA: Stress-related serotonergic systems: implications for symptomatology of anxiety and affective disorders. Cell Mol Neurobiol 2012, 32:695-708.
• [69]Dallman MF, Akana SF, Strack AM, Scribner KS, Pecoraro N, La Fleur SE, Houshyar H, Gomez F: Chronic stress-induced effects of corticosterone on brain: direct and indirect. Ann N Y Acad Sci 2004, 1018:141-150.
• [70]Morilak DA, Barrera G, Echevarria DJ, Garcia AS, Hernandez A, Ma S, Petre CO: Role of brain norepinephrine in the behavioral response to stress. Prog Neuropsychopharmacol Biol Psychiatry 2005, 29:1214-1224.
• [71]Morse DE: Neuroendocrine responses to nicotine and stress: enhancement of peripheral stress responses by the administration of nicotine. Psychopharmacology (Berl) 1989, 98:539-543.
• [72]Cools R, D'Esposito M: Inverted-U-shaped dopamine actions on human working memory and cognitive control. Biol Psychiatry 2011, 69:113-125.
• [73]Livingstone PD, Srinivasan J, Kew JN, Dawson LA, Gotti C, Moretti M, Shoaib M, Wonnacott S: alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal cortex. Eur J Neurosci 2009, 29:539-550.
• [74]Timofeeva OA, Levin ED: Glutamate and nicotinic receptor interactions in working memory: importance for the cognitive impairment of schizophrenia. Neuroscience 2011, 195:21-36.
• [75]Issa AM, Rowe W, Gauthier S, Meaney MJ: Hypothalamic-pituitary-adrenal activity in aged, cognitively impaired and cognitively unimpaired rats. J Neurosci 1990, 10:3247-3254.
• [76]Weiss IC, Pryce CR, Jongen-Rêlo AL, Nanz-Bahr NI, Feldon J: Effect of social isolation on stress-related behavioural and neuroendocrine state in the rat. Behav Brain Res 2004, 152:279-295.
• [77]Troakes C, Ingram CD: Anxiety behaviour of the male rat on the elevated plus maze: associated regional increase in c-fos mRNA expression and modulation by early maternal separation. Stress 2009, 12:362-369.
• [78]Matsuo N, Yamasaki N, Ohira K, Takao K, Toyama K, Eguchi M, Yamaguchi S, Miyakawa T: Neural activity changes underlying the working memory deficit in alpha-CaMKII heterozygous knockout mice. Front Behav Neurosci 2009, 3:20.
• [79]Porter AC, Sauer JM, Knierman MD, Becker GW, Berna MJ, Bao J, Nomikos GG, Carter P, Bymaster FP, Leese AB, Felder CC: Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J Pharmacol Exp Ther 2002, 301:1020-1024.
• [80]George TP, Verrico CD, Roth RH: Effects of repeated nicotine pre-treatment on mesoprefrontal dopaminergic and behavioral responses to acute footshock stress. Brain Res 1998, 801:36-49.
• [81]Verrico CD, Jentsch JD, Roth RH: Persistent and anatomically selective reduction in prefrontal cortical dopamine metabolism after repeated, intermittent cannabinoid administration to rats. Synapse 2003, 49:61-66.
• [82]Viveros MP, Marco EM, File SE: Nicotine and cannabinoids: parallels, contrasts and interactions. Neurosci Biobehav Rev 2006, 30:1161-1181.
• [83]Braida D, Limonta V, Malabarba L, Zani A, Sala M: 5-HT1A receptors are involved in the anxiolytic effect of Delta9-tetrahydrocannabinol and AM 404, the anandamide transport inhibitor, in Sprague–Dawley rats. Eur J Pharmacol 2007, 555:156-163.
• [84]Haller J, Mátyás F, Soproni K, Varga B, Barsy B, Németh B, Mikics E, Freund TF, Hájos N: Correlated species differences in the effects of cannabinoid ligands on anxiety and on GABAergic and glutamatergic synaptic transmission. Eur J Neurosci 2007, 25:2445-2456.
• [85]Genn RF, Tucci S, Marco EM, Viveros MP, File SE: Unconditioned and conditioned anxiogenic effects of the cannabinoid receptor agonist CP 55,940 in the social interaction test. Pharmacol Biochem Behav 2004, 77:567-573.
• [86]García-Gutiérrez MS, Manzanares J: Overexpression of CB2 cannabinoid receptors decreased vulnerability to anxiety and impaired anxiolytic action of alprazolam in mice. J Psychopharmacol 2011, 25:111-120.
• [87]García-Gutiérrez MS, García-Bueno B, Zoppi S, Leza JC, Manzanares J: Chronic blockade of cannabinoid CB2 receptors induces anxiolytic-like actions associated with alterations in GABA(A) receptors. Br J Pharmacol 2012, 165:951-964.
• [88]Pertwee RG: GPR55: a new member of the cannabinoid receptor clan? Br J Pharmacol 2007, 152:984-986.
• [89]Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ: The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 2007, 152:1092-1101.
• [90]Kapur A, Zhao P, Sharir H, Bai Y, Caron MG, Barak LS, Abood ME: Atypical responsiveness of the orphan receptor GPR55 to cannabinoid ligands. J Biol Chem 2009, 284:29817-29827.
• [91]Sharir H, Console-Bram L, Mundy C, Popoff SN, Kapur A, Abood ME: The endocannabinoids anandamide and virodhamine modulate the activity of the candidate cannabinoid receptor GPR55. J Neuroimmune Pharmacol 2012, 7:856-865.
• [92]de Fonseca FR, Schneider M: The endogenous cannabinoid system and drug addiction: 20 years after the discovery of the CB1 receptor. Addict Biol 2008, 13:143-146.