Abstract
Rationale
Nicotine improves cognitive function in a number of animal models including rats, mice, monkeys, and recently, zebrafish. The zebrafish model allows higher throughput and ease in discovering mechanisms of cognitive improvement.
Materials and methods
To further characterize the neural bases of nicotine effects on learning in zebrafish, we determined changes in dopaminergic systems that accompany nicotine-enhanced learning.
Results
Nicotine improved learning and increased brain levels of dihydroxyphenylacetic acid (DOPAC), the primary dopamine metabolite. There was a significant correlation between choice accuracy and DOPAC levels. The nicotinic antagonist mecamylamine blocked the nicotine-induced increase in DOPAC concentrations, in line with our previous finding that mecamylamine reversed nicotine-induced learning improvement.
Conclusions
Dopamine systems are related to learning in zebrafish; nicotine exposure increases both learning rates and DOPAC levels; and nicotinic antagonist administration blocks nicotine-induced rises in DOPAC concentrations. Rapid cognitive assessment of drugs with zebrafish could serve as a useful screening tool for the development of new therapeutics for cognitive dysfunction.
Similar content being viewed by others
References
Anichtchik OV, Kaslin J, Peitsaro N, Scheinin M, Panula P (2004) Neurochemical and behavioural changes in zebrafish Danio rerio after systemic administration of 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J Neurochem 88:443–453
Arthur D, Levin ED (2001) Spatial and non-spatial discrimination learning in zebrafish. Anim Cogn 4:125–131
Bilotta J, Barnett JA, Hancock L, Saszik S (2004) Ethanol exposure alters zebrafish development: a novel model of fetal alcohol syndrome. Neurotoxicol Teratol 26:737–743
Boehmler W, Obrecht-Pflumio S, Canfield V, Thisse C, Thisse B, Levenson R (2004) Evolution and expression of D2 and D3 dopamine receptor genes in zebrafish. Dev Dyn 230:481–493
Boehmler W, Carr T, Thisse C, Thisse B, Canfield VA, Levenson R (2007) D4 Dopamine receptor genes of zebrafish and effects of the antipsychotic clozapine on larval swimming behaviour. Genes Brain Behav 6:155–166
Bretaud S, Lee S, Guo S (2004) Sensitivity of zebrafish to environmental toxins implicated in Parkinson’s disease. Neurotoxicol Teratol 26:857–864
Buccafusco JJ, Jackson WJ (1991) Beneficial effects of nicotine administered prior to a delayed matching-to-sample task in young and aged monkeys. Neurobiol Aging 12:233–238
Carvan MJ 3rd, Loucks E, Weber DN, Williams FE (2004) Ethanol effects on the developing zebrafish: neurobehavior and skeletal morphogenesis. Neurotoxicol Teratol 26:757–768
Clarke PB, Schwartz RD, Paul SM, Pert CB, Pert A (1985) Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-alpha-bungarotoxin. J Neurosci 5:1307–1315
Clemente D, Porteros A, Weruaga E, Alonso JR, Arenzana FJ, Aijon J, Arevalo R (2004) Cholinergic elements in the zebrafish central nervous system: histochemical and immunohistochemical analysis. J Comp Neurol 474:75–107
Dunnett SB, Martel FL (1990) Proactive interference effects on short-term memory in rats: 1. Basic parameters and drug effects. Behav Neurosci 104:655–665
Holzschuh J, Ryu S, Aberger F, Driever W (2001) Dopamine transporter expression distinguishes dopaminergic neurons from other catecholaminergic neurons in the developing zebrafish embryo. Mech Dev 101:237–243
Kaethner RJ, Stuermer CA (1997) Dynamics of process formation during differentiation of tectal neurons in embryonic zebrafish. J Neurobiol 32:627–639
Lam CS, Korzh V, Strahle U (2005) Zebrafish embryos are susceptible to the dopaminergic neurotoxin MPTP. Eur J Neurosci 21:1758–1762
Levin ED, Chen E (2004) Nicotinic involvement in memory function in zebrafish. Neurotoxicol Teratol 26:731–735
Levin ED, Rezvani A (2002) Nicotinic treatment for cognitive dysfunction. Current Drug Targets CNS Neurol Disord 1:423–431
Levin ED, Simon BB (1998) Nicotinic acetylcholine involvement in cognitive function in animals. Psychopharmacology 138:217–230
Levin ED, Crysthansis E, Yacisin K, Linney E (2003) Chlorpyrifos exposure of developing zebrafish: effects on survival and long-term effects on response latency and spatial discrimination. Neurotoxicol Teratol 25:51–57
Levin ED, Limpuangthip J, Rachakonda T, Peterson M (2006) Timing of nicotine effects on learning in zebrafish. Psychopharmacology 184:547–552
Li P, Shah S, Huang L, Carr AL, Gao Y, Thisse C, Thisse B, Li L (2007) Cloning and spatial and temporal expression of the zebrafish dopamine D1 receptor. Dev Dyn 236:1339–1346
McKinley ET, Baranowski TC, Blavo DO, Cato C, Doan TN, Rubinstein AL (2005) Neuroprotection of MPTP-induced toxicity in zebrafish dopaminergic neurons. Brain Res Mol Brain Res 141:128–137
Mundy WR, Iwamoto ET (1988) Nicotine impairs acquisition of radial-arm maze performance in rats. Psychopharmacology 94:267–274
Newhouse PA, Kelton M (2000) Nicotinic systems in central nervous systems disease: degenerative disorders and beyond. Pharm Acta Helv 74:91–101
Newhouse PA, Potter A, Levin ED (1997) Nicotinic system involvement in Alzheimer’s and Parkinson’s diseases: implications for therapeutics. Drugs Aging 11:206–228
Phillips AG, Ahn S, Floresco SB (2004) Magnitude of dopamine release in medial prefrontal cortex predicts accuracy of memory on a delayed response task. J Neurosci 24:547–553
Reimers MJ, Flockton AR, Tanguay RL (2004) Ethanol- and acetaldehyde-mediated developmental toxicity in zebrafish. Neurotoxicol Teratol 26:769–781
Rossetti ZL, Carboni S (2005) Noradrenaline and dopamine elevations in the rat prefrontal cortex in spatial working memory. J Neurosci 25:2322–2329
Singer S, Rossi S, Verzosa S, Hashim A, Lonow R, Cooper T, Sershen H, Lajtha A (2004) Nicotine-induced changes in neurotransmitter levels in brain areas associated with cognitive function. Neurochem Res 29:1779–1792
Welzl H, Alessandri B, Oettinger R, Bättig K (1988) The effects of long-term nicotine treatment on locomotion, exploration and memory in young and old rats. Psychopharmacology 96:317–323
Wullimann MF, Rupp B, Reichert H (1996) Neuroanatomy of the zebrafish brain: a topological atlas. Birkhauser, Basel
Zirger JM, Beattie CE, McKay DB, Boyd RT (2003) Cloning and expression of zebrafish neuronal nicotinic acetylcholine receptors. Gene Expr Patterns 3:747–754
Acknowledgement
Research support was provided by the Duke University Superfund Basic Research Center (NIH ES010356).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Eddins, D., Petro, A., Williams, P. et al. Nicotine effects on learning in zebrafish: the role of dopaminergic systems. Psychopharmacology 202, 103–109 (2009). https://doi.org/10.1007/s00213-008-1287-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-008-1287-4