Effects of Administration of Perinatal Bupropion on the Population Spike Amplitude in Neonatal Rat Hippocampal Slices

Document Type: Original Article

Authors

1 Department of Biology, Faculty of Science, Urmia University, Urmia, Iran

2 Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

Abstract

Objective(s)
Bupropion is an atypical antidepressant that is widely used in smoke cessation under FDA approval. The study of synaptic effects of bupropion can help to finding out its mechanism(s) for stopping nicotine dependence. In this study the effects of perinatal bupropion on the population spike (PS) amplitude of neonates were investigated.
Materials and Methods
Hippocampal slices were prepared from 18-25 days old rat pups. The experimental groups included control and bupropion-treated. Bupropion (40 mg/Kg, i.p.) was applied daily in perinatal period as pre-treatment. Due to the studying acute effects, bupropion was also added to the perfusion medium (10, 50, 200 pM for 30 min). The evoked PS was recorded from pyramidal layer of CA1 area, following stimulation of Schaffer collaterals. Results
A concentration of 10 pM bupropion had no significant effects on the PS amplitude. The 50 pM concentration of bupropion reduced the amplitude of responses in 50% of the studied cases. At a concentration of 200 pM, the recorded PS amplitudes were reduced in all slices (n= 22). Amplitude was completely abolished in 8 out of the 22 slices. The decrease of the PS amplitude was found to be more in the non-pre-treated slices than in the pre-treated slices when both were perfused with 200 pM bupropion.
Conclusion
The results showed the perinatal exposure to bupropion and its acute effects while indicating that at concentrations of 50 and 200 pM bupropion reduced the PS amplitude. It was also found that there was evidence of synaptic adaptation in comparison of bupropion-treated and non-treated slices whereas they were both perfused with 200 pM.

Keywords


1.Hayford KE, Patten CA, Rummans TA, Schroeder DR, Offord KP, Croghan IT, et al. Efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism. Br J Psychiatry 1999; 174:173-178.

2.Balfour DJ. The pharmacology underlying pharmacotherapy for tobacco dependence: a focus on bupropion. Int J Clin Pract 2001; 55:53-57.

3. Ascher JA, Cole JO, Colin JN, Feighner JP, Ferris RM, Fibiger HC, et al. Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry 1995; 56:395-401.

4.Dwoskin LP, Rauhut AS, King- Pospisil KA, Bardo MT. Review of the pharmacology and clinical profile of Bupropion, an antidepressant and tobacco use cessation agent. CNS Drug Rev 2006; 12:178-207.

5.Ferris RM, Beaman OJ. Bupropion: a new antidepressant drug, the mechanism of action of which is not associated with down-regulation of postsynaptic beta-adrenergic, serotonergic (5-HT2), alpha 2-adrenergic, imipramine and dopaminergic receptors in brain. Neuropharmacology 1983; 22:1257-1267. 

6.Dong J, Blier P. Modification of norepinephrine and serotonin, but not dopamine, neuron firing by sustained bupropion treatment. Psychopharmacology 2001; 155:52-57.

7.ElMansari M, Ghanbari R, Janssen S, Blier P. Sustained administration of bupropion alters the neuronal activity of serotonin, norepinephrine but not dopamine neurons in the rat brain. Neuropharmacolology 2008; 55:1191-1198.

8.Li SX, Perry KW, Wong DT. Influence of fluoxetine on the ability of bupropion to modulate extracellular dopamine and norepinephrine concentrations in three mesocorticolimbic areas of rats. Neuropharmacology 2002; 42:181-190.

9.Mansvelder HD, Fagen ZM, Chang B, Mitchum R, Mc Gehee DS. Bupropion inhibits the cellular effects of nicotine in the ventral tegmental area. Biochem Pharmacol 2007; 74:1283-1291.

10.Placzek AN, Zhang TA, Dani JA. Nicotinic mechanisms influencing synaptic plasticity in the hippocampus. Acta Pharmacol Sin 2009; 30:752-760.

11.Kauer JA. Learning mechanisms in addiction: synaptic plasticity in the ventral tegmental area as a result of exposure to drugs of abuse. Annu Rev Physiol 2004; 66:447-475.

12.Garrett BE, Rose CA, Henningfield JE. Tobacco addiction and pharmacological interventions. Expert Opin Pharmacolther 2001; 2:1545-1555.

13.Dani JA, De Biasi M. Synaptic plasticity and nicotine addiction. Neuron 2001; 31:349-352.

14.Jones S, Bonci A. Synaptic plasticity and drug addiction. Curr Opin Pharmacol 2005; 5:20-25.

15.Gould TJ. Nicotine and hippocampus- dependent learning. Mol Neurobiol 2006; 34:93-107.

16.Kenney JW, Gould TJ. Modulation of hippocampus-dependent learning and synaptic plasticity by nicotine. Mol Neurobiol 2008; 38:101- 121.

17.Watanabe Y, Saito H, Abe K. Tricyclic antidepressants block NMDA receptor-mediated synaptic responses and induction of long term potentiation in rat hippocampal slices. Neuropharmacology 1993; 32:479- 486.

18.Stewart CA, Reid IC. Repeated ECS and fluoxetine administration have equivalent effects on hippocampal synaptic plasticity. Psychopharmacology 2000; 148:217-223.

19.Birnstiel S, Haas HL. Acute effects of antidepressant drugs on long-term potentiation (LTP) in rat Hippocampal slices. Naunyn-Schmiedebergs Arch Pharmacol 1991; 344:79-83.

20.Crawley JN, Gerfen CR, Rogawski MA, Sibley DR, Skolnick P, Wray S. Synaptic plasticity in the hippocampal slice preparation. In: Taylor GP. editors. Current protocols in neurosci John Wiley & Sons, Inc.; 2003.

21.Wang T, Kass IS. Preparation of brain slices. In: Rayne RC. editor. Methods in molecular biology Totowa: Humana Press Inc; 1997.p.1-14.

22.Massicotte G, Bernard J,Ohayon M. Chronic effects of trimipramine, an antidepressant, on hippocampal synaptic plasticity. Behav Neural Biol 1993; 59:100-106.

23.Langosch JM, Walden J. Affects of the atypical antidepressant trimipramine on neuronal excitability and long¬term potentiation in guinea pig hippocampal slices. Progress in Neuro- Psychopharmacol Biological Psychia 2002; 26:299-302.

24.Stewart CA, Reid IC. Antidepressant mechanisms: functional and molecular correlates of excitatory amino acid neurotransmission. Mol Psychiatry 2002; 7:15-22.

25.D’Sa C, Duman RS. Antidepressants and neuroplasticity. Bipolar Disord 2002; 4:183-194.

26.Duman RS, Malberg J, Thome J. Neural plasticity to stress and antidepressant treatment. Biol Psychiatry 1999; 46:1181-1191.

27.Castren E. Neurotrophic effects of antidepressant drugs. Curr Opin Pharmacol 2004; 4:58-64.

28.Zahorodna A, Bijak M. An antidepressant induced decrease in the responsiveness of Hippocampal neurons to group I metabotropic glutamate receptor activation. Eur J Pharmacol 1999; 386:173-179.

29.Yashiro K, Philpot BD. Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity. Neuropharmacology 2008; 55:1081-1094.

30.Bobula B, Tokarski K, Hess G. Repeated administration of antidepressants decreases field potentials in rat frontal cortex. Neuroscience 2003; 120:765-769.

31.Popoli M, Gennarelli M, Racagni G. Modulation of synaptic plasticity by stress and antidepressants. Bipolar Disord 2002; 4: 166-182.

32.Reid IC, Stewart CA. Brain plasticity and antidepressant treatments: new cells, new connections. Neurotox Res 2004; 6:483-491.

33.Mc Bain CJ, Freund TF, Mody I. Glutamatergic synapses on to Hippocampal interneuron: precision timing without lasting plasticity. Trends Neurosci 1999; 22:228-235.

34.Baskys A, Wang S, Remington G, Wotjtowicz JM. Haloperidol and loxapine but not clozapine increase synaptic responses in the hippocampus. Eur J Pharmacol 1993; 235:305-307.

35.Chen Long, Charles R Yang. Interaction of dopamine D1 and NMDA receptors mediates acute clozapine potentiation of glutamate EPSPs in rat prefrontal cortex. J Neurophysiol 2002; 87:2324-2336.