Skip to main content
SpringerLink
Log in

Bupropion effects on aggressiveness and anxiety in OF1 male mice

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Bupropion is an antidepressant drug that is being used to help in giving up smoking. Its behavioral effects have been evaluated in different animal models, although limited information is available regarding its effects on aggressiveness, anxiety and exploratory behavior.

Objectives

Evaluate acute effects of bupropion on locomotor activity, isolation-induced aggression, hole-board and elevated plus-maze tests in OF1 male mice.

Methods

In the first experiment, effects of bupropion (2.5, 5, 10, 20 and 40 mg/kg) on locomotion were evaluated. In the second experiment, isolation-induced aggression was assessed in isolated male mice previously classified as short attack latency (SL) and long attack latency (LL). Mice were treated with bupropion or vehicle and confronted with standard opponents for 10 min. In experiments 3 and 4, mice were treated with bupropion or vehicle and 30 min later examined in the plus-maze or in the hole-board apparatus.

Results

In the actimeter, bupropion induced a dose-dependent increase in locomotion. During agonistic encounters, bupropion (10 mg/kg and 40 mg/kg) increased time devoted to attack in LL mice. In the plus-maze, no significant differences were found between bupropion-treated and vehicle-treated mice in the percentage of entries or time spent in open arms. In the hole-board, the highest dose of bupropion (40 mg/kg) significantly decreased number of head-dips and increased latency to the first head-dip.

Conclusions

During agonistic encounters the two sub-groups of mice (SL and LL) may display differential sensitivity in drug-induced changes on aggressiveness, since bupropion increased attack only in mice with “long attack latency” in the pre-screening test. In the plus-maze, this drug does not seem to have specific actions on anxiety and in the hole-board a high dose had similar effects to those induced by anxiogenic drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Ascher JA, Cole JO, Colin JN, Feighner JP, Ferris RM, Fibiger HC, Golden RN, Martin P, Potter WZ, Richelson E, Sulser F (1995) Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry 56:395–401

    CAS  PubMed  Google Scholar 

  • Baizman ER, Ezrin AM, Ferrari RA, Luttinger D (1987) Pharmacologic profile of fezolamine fumarate: a nontricyclic antidepressant in animal models. J Pharmacol Exp Ther 243:40–54

    CAS  PubMed  Google Scholar 

  • Barros DM, Izquierdo LA, Medina JH, Izquierdo I (2002) Bupropion and setraline enhance retrieval of recent and long-term memory in rats. Behav Pharmacol 13:215–220

    CAS  PubMed  Google Scholar 

  • Belzung C, Griebel G (2001) Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav Brain Res 125:141–149

    Article  CAS  PubMed  Google Scholar 

  • Boissier JR, Simon P (1962) La reaction d’exploration chez la souris. Therapie 17:1225–1232

    CAS  PubMed  Google Scholar 

  • Borsini F, Podhorna J, Marazziti D (2002) Do animal models of anxiety predict anxiolytic-like effects of antidepressants? Psychopharmacology 163:121–141

    Article  CAS  PubMed  Google Scholar 

  • Brain PF, Benton D, Childs G, Parmigiani S (1981) The effect of the opponent in tests of murine aggression. Behav Proc 6:319–328

    Article  Google Scholar 

  • Comissaris RL, Ellis DM, Hill TJ, Schefke DM, Becker CA, Fontana DJ (1990) Chronic antidepressant and clonidine treatment effects on conflict behavior in the rat. Pharmacol Biochem Behav 37:167–176

    Article  PubMed  Google Scholar 

  • Cooper BR, Hester TJ, Maxwell RA (1980) Behavioral and biochemical effects of the antidepressant bupropion (Wellbutrin): evidence for selective blockade of dopamine uptake in vivo. J Pharmacol Exp Ther 215:127–134

    CAS  PubMed  Google Scholar 

  • Cryan JF, Bruijnzeel AW, Skjei KL, Merkou A (2003) Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat. Psychopharmacology 168:347–358

    Article  CAS  PubMed  Google Scholar 

  • Cutler MG (1994) Anxiolytic drugs: does ethopharmacological analysis indicate commonalities in their mode of action? Ethol Psychopharmacol 4:45–58

    Google Scholar 

  • David DJP, Renard CE, Jolliet P, Hascoët M, Bourin M (2003) Antidepressant-like effects in various mice strains in the forced swimming test. Psychopharmacology 166:373–382

    CAS  PubMed  Google Scholar 

  • De Boer SF, Koolhaas JM (2003) Defensive burying in rodents: ethology, neurobiology and psychopharmacology. Eur J Pharmacol 463:145–161

    Article  CAS  PubMed  Google Scholar 

  • Dong J, Blier P (2001) Modification of norepinephrine and serotonin, but not dopamine, neuron firing by sustained bupropion treatment. Psychopharmacology 155:52–57

    Article  CAS  PubMed  Google Scholar 

  • Elliott BM, Faraday MM, Phillips JM, Grunberg NE (2004) Effects of nicotine on elevated plus maze and locomotor activity in male and female adolescent and adult rats. Pharmacol Biochem Behav 77:21–28

    Article  CAS  PubMed  Google Scholar 

  • Espejo EF (1997) Structure of the mouse behavior on the elevated plus-maze test of anxiety. Behav Brain Res 86:105–112

    Article  PubMed  Google Scholar 

  • Feldker DEM, Datson NA, Veenema AH, Meulmeester E, de Kloet ER, Vreugdenhill E (2003) Serial analysis of gene expression predicts structural differences in hippocampus of long attack latency and short attack latency mice. Eur J Neurosci 17:379–387

    Article  PubMed  Google Scholar 

  • Felip CM, Rodriguez-Arias M, Aguilar MA, Miñarro J (2001) Antiaggressive and motor effects of the DA release inhibitor CGS 0746B. Aggress Behav 27:382–390

    Article  CAS  Google Scholar 

  • File SE (1992) Behavioural detection of anxiolytic action. In: Elliott JM, Heal DJ, Heal DJ, Marsden CA (eds) Experimental approaches to anxiety and depression. Wiley, Chichester, pp 25–44

    Google Scholar 

  • File SE, Seth P (2003) A review of 25 years of the social interaction test. Eur J Pharmacol 463:35–53

    Article  CAS  PubMed  Google Scholar 

  • Fryer JD, Lukas RJ (1999) Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine and ibogaine. J Pharmacol Exp Ther 288:88–92

    CAS  PubMed  Google Scholar 

  • Hays JT, Ebbert JO (2003) Bupropion for the treatment of tobacco dependence: guidelines for balancing risks and benefits. CNS Drugs 17:71–83

    CAS  PubMed  Google Scholar 

  • Holmes A, Rodgers RJ (2003) Prior exposure to the elevated plus-maze sensitizes mice to acute behavioral effects of fluoxetine and phenelzine. Eur J Pharmacol 459:221–230

    Article  CAS  PubMed  Google Scholar 

  • Hughes JR, Stead LF, Lancaster T (2003) Antidepressants for smoking cessation (Cochrane review). Cochrane Database Syst Rev 2. CD000031

  • Klimek V, Nowak G, Czyrak A (1985) Central effects of repeated treatment with bupropion. Pol J Pharmacol Phar 37:243–252

    CAS  Google Scholar 

  • Lake JR, Montellano AL, Presley SE, Meyer-Paal RL, Perales BA, Oliver M, Malin DH (2001) Acute-bupropion dose-dependently reduces nicotine abstinence syndrome in the rat. Soc Neurosci Abstr 27:15

    Google Scholar 

  • Lerman C, Roth D, Kaufmann V, Audrain J, Hawk L, Liu A, Niaura R, Epstein L (2002) Mediating mechanisms for the impact of bupropion in smoking cessation treatment. Drug Alcohol Depend 67:219–223

    Article  CAS  PubMed  Google Scholar 

  • Li S, Perry KW, Wong DT (2002) Influence of fluoxetine on the ability of bupropion to modulate extracellular dopamine and norepinephrine concentrations in three mesocorticolimbic areas of rats. Neuropharmacology 42:181–190

    Article  CAS  PubMed  Google Scholar 

  • Lumley LA, Robison CL, Slusher BS, Wozniak K, Dawood M, Meyerhoff JL (2004) Reduced isolation-induced aggressiveness in mice following NAALADase inhibition. Psychopharmacology 171:375–381

    Article  CAS  PubMed  Google Scholar 

  • Martínez-Sanchis S, Arnedo MT, Salvador A, Moya-Albiol L, González-Bono E (2003) Effects of chronic administration with high doses of testosterone propionate on behavioral and physiological parameters in mice with differing basal aggressiveness. Aggress Behav 29:173–189

    Article  Google Scholar 

  • Miczek KA, Maxson SC, Fish EW, Faccidomo S (2001) Aggressive behavioral phenotypes in mice. Behav Brain Res 125:167–181

    Article  CAS  PubMed  Google Scholar 

  • Miczek KA, Fish EW, de Bold JF, de Almeida RMM (2002) Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamin and γ-aminobutyric acid systems. Psychopharmacology 163:434–458

    Article  CAS  PubMed  Google Scholar 

  • Miller DK, Sumithran SP, Dwoskin LP (2002) Bupropion inhibits nicotine-evoked [(3)H]overflow from rat striatal slices preloaded with [(3)H]dopamine and from rat hippocampal slices preloaded with [(3)H]norepinephrine. J Pharmacol Exp Ther 302:1113–1122

    Article  CAS  PubMed  Google Scholar 

  • Moragrega I, Carrasco MC, Vicens P, Redolat R (2003) Spatial learning in male mice with different level of aggressiveness: effects of housing conditions and nicotine administration. Behav Brain Res 147:1–8

    Article  CAS  PubMed  Google Scholar 

  • Navarro JF, Rivera A, Maldonado E, Cavas M, de la Calle A (2004) Anxiogenic-like activity of 3,4-methylenedioxy-metamphetamine (“Ecstasy”) in the social interaction test is accompanied by an increase of c-fos expression in mice amygdale. Progress Neuro-Psychopharmacol Biol Psychiatry 28:249–254

    Article  CAS  Google Scholar 

  • Nakawaga T, Ukai K, Ohyama T, Gomita Y, Okamura H (1997) Effects of dopaminergic agents on reversal of reserpine-induced impairment in conditioned avoidance response in rats. Pharmacol Biochem Behav 58:829–836

    Article  PubMed  Google Scholar 

  • Njung’e K, Handley SL (1991) Evaluation of marble-burying behavior as a model of anxiety. Pharmacol Biochem Behav 38:63–67

    Article  CAS  PubMed  Google Scholar 

  • Ohl F (2003) Testing for anxiety. Clin Neurosci Res 3:233–238

    Article  Google Scholar 

  • Pellow S, File SE (1986) Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 24:525–529

    Article  CAS  PubMed  Google Scholar 

  • Rauhut AS, Neugebauer N, Deoskin LP, Bardo NT (2004) Effect of bupropion on nicotine self-administration in rats. Psychopharmacology 169:1–9

    Article  Google Scholar 

  • Redolat R, Brain OF, Simón VM (1991) Sulpiride has an antiaggressive effect in mice without markedly depressing motor activity. Neuropharmacology 1:41–46

    Article  Google Scholar 

  • Redolat R, Oterino MC, Carrasco MC, Berry MS, Brain PF (2000) Effects of acute administration of nicotine and lobeline on agonistic encounters in male mice. Aggress Behav 26:376–385

    Article  CAS  Google Scholar 

  • Richmond R, Zwar N (2003) Review of bupropion for smoking cessation. Drug Alcohol Rev 22:203–220

    Article  PubMed  Google Scholar 

  • Ripoll N, David DJP, Dailly E (2003) Antidepressant-like effect in various mice strains in the tail suspension test. Behav Brain Res 143:193–200

    Article  CAS  PubMed  Google Scholar 

  • Rodgers RJ, Cole JC (1993) Influence of social isolation, gender, strain and prior novelty on plus-maze behaviour in mice. Physiol Behav 54:729–736

    Article  CAS  PubMed  Google Scholar 

  • Rodgers RJ, Cole JC (1994) The elevated plus-maze: pharmacology, methodology and ethology. In: Cooper SJ, Hendrie CA (eds) Ethology and psychopharmacology. Wiley, Chichester, pp 9–44

    Google Scholar 

  • Rodgers RJ, Johnson NJT, Carr J, Hodgson TP (1997) Resistance of experimentally induced changes in murine plus-maze behaviour to altered retest conditions. Behav Brain Res 86:71–77

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez-Arias M, Miñarro J, Aguilar MA, Simon VM (1998) Effects of risperidone and SCH 23390 on isolation-induced aggression in male mice. Eur Neuropsychopharmacol 8:95–103

    Article  CAS  PubMed  Google Scholar 

  • Shiffman S, Johnston JA, Khayrallah M, Elash CA, Gwaltney CJ, Paty JA, Gnys M, Evoniuk G, DeVeaugh-Geiss J (2000) The effect of bupropion on nicotine craving and withdrawal. Psychopharmacology 148:33–40

    Article  CAS  PubMed  Google Scholar 

  • Shoaib M, Sidhpura N, Shafait S (2003) Investigating the actions of bupropion on dependence-related effects of nicotine in rats. Psychopharmacology 165:405–412

    CAS  PubMed  Google Scholar 

  • Slemmer JE, Martin BR, Damaj MI (2000) Bupropion is a nicotinic antagonist. J Pharmacol Exp Ther 295:321–327

    CAS  PubMed  Google Scholar 

  • Sluyter F, Korte SM, Bohus B, van Oortmerssen GA (1996) Behavioral stress response of genetically selected aggressive and nonaggressive wild house mice in the shock-probe/defensive burying test. Pharmacol Biochem Behav 54:113–116

    Article  CAS  PubMed  Google Scholar 

  • Strickland JA, Da Vanzo JP (1986) Must antidepressants be anticholinergic to inhibit muricide? Pharmacol Biochem Behav 24:135–137

    Article  CAS  PubMed  Google Scholar 

  • Takeda T, Tsuji M, Matsumiya T (1998) Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur J Pharmacol 350:21–29

    Article  CAS  PubMed  Google Scholar 

  • Tsuji M, Takeda H, Matsumiya T (2000) Different effects of 5-HT1A receptor agonist and benzodiacepine anxiolytics on the emotional state of naive and stressed mice: a study using the hole-board test. Psychopharmacology 152:157–166

    Article  CAS  PubMed  Google Scholar 

  • Vaglenova J, Birru S, Pandiella NM, Breese CR (2004) An assessment of the long-term developmental and behavioural teratogenicity of prenatal nicotine exposure. Behav Brain Res 150:159–170

    Article  CAS  PubMed  Google Scholar 

  • Van Gaalen MM, Steckler T (2000) Behavioral analysis of four mouse strains in an anxiety test battery. Behav Brain Res 115:95–106

    Article  PubMed  Google Scholar 

  • Veenema AH, Meijer OC, de Kloet ER, Koolhaas JM, Bohus BG (2003) Differences in basal and stress-induced HPA regulation in wild house mice selected for high and low aggression. Horm Behav 43:197–204

    Article  CAS  PubMed  Google Scholar 

  • Wall PM, Messier C (2000) Ethological confirmatory factor analysis of anxiety-like behaviour in the murine elevated plus-maze. Behav Brain Res 114:199–212

    Article  CAS  PubMed  Google Scholar 

  • Weiss SM, Wadsworth G, Fletcher A, Dourish CT (1998) Utility of ethological analysis to overcome locomotor confounds in elevated models of anxiety. Neurosci Biobehav Rev 23:265–271

    Article  CAS  PubMed  Google Scholar 

  • Young R, Glennon RA (2002) Nicotine and bupropion share a similar discriminative stimulus effect. Eur J Pharmacol 443:113–118

    Article  CAS  PubMed  Google Scholar 

  • Zarrindast MR, Hosseini-Nia T (1988) Anorectic and behavioural effects of bupropion. Gen Pharmacol 19:201–204

    Article  CAS  PubMed  Google Scholar 

  • Zarrindast MR, Hodjati MR, Pejhan A, Soleimannejad E (1996) Bupropion induces sniffing: a possible dopaminergic mechanism. Eur Neuropsychopharmacol 6:299–303

    Article  CAS  PubMed  Google Scholar 

  • Zarrindast M, Momayoun H, Babaie A, Etminani A, Gharib B (2000) Involvement of adrenergic and cholinergic systems in nicotine-induced anxiogenesis in mice. Eur J Pharmacol 407:145–158

    Article  CAS  PubMed  Google Scholar 

  • Zarrindast M, Rostami P, Sadeghi-Hariri M (2001) GABAA but not GABAB receptor stimulation induces antianxiety profile in rats. Pharmacol Biochem Behav 69:9–15

    Article  CAS  PubMed  Google Scholar 

  • Zocchi A, Varnier G, Arban R, Griffante C, Zanetti L, Bettelini L, Marchi M, Gerrard PA, Corsi M (2003) Effects of antidepressant drugs and GR 205171, an neurokinin-1 (NK1) receptor antagonist, on the response in the forced swim test and on monoamine extracellular levels in the frontal cortex of the mouse. Neurosci Lett 345:73–76

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from “Ministerio de Ciencia y Tecnología” (I+D+I) (Spain) and FEDER funds. Grant number: BSN2003-02780. All experiments comply with the current laws in Spain.

Author information

Authors and Affiliations

  1. Area de Psicobiología, Facultad de Psicología, Universitat de València, Blasco Ibañez, 21, 46010, Valencia, Spain

    Rosa Redolat, M. Carmen Gómez & M. Carmen Carrasco

  2. Area de Psicobiología, Facultad de Ciencias de la Educación y Psicología, Universitat Rovira i Virgili, Carretera de Valls s/n, 43007, Tarragona, Spain

    Paloma Vicens

Authors
  1. Rosa Redolat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Carmen Gómez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paloma Vicens
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Carmen Carrasco
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rosa Redolat.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Redolat, R., Gómez, M.C., Vicens, P. et al. Bupropion effects on aggressiveness and anxiety in OF1 male mice. Psychopharmacology 177, 418–427 (2005). https://doi.org/10.1007/s00213-004-1965-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-004-1965-9

Keywords

Search

Navigation