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Enhancement of serotonergic and noradrenergic neurotransmission in the rat hippocampus by sustained administration of bupropion

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Abstract

Rationale

Previous studies reported that bupropion, an effective antidepressant, exerts modulatory actions on serotonin (5-HT) and norepinephrine (NE) neurons.

Objectives

This study examined effects of bupropion administration on 5-HT and NE neurotransmission in hippocampus.

Methods

Electrophysiological recordings were obtained from anesthetized Sprague–Dawley rats. Subcutaneously implanted minipumps delivered saline or bupropion (30 mg/kg/day) for 2 and 14 days.

Results

Although sustained bupropion administration did not alter the sensitivity of 5-HT1A and α2-adrenergic receptors, the tonic activation of postsynaptic 5-HT1A receptors by endogenous 5-HT was enhanced in 14-day bupropion-treated rats to a greater extent than in the 2-day and control rats, as revealed by the greater disinhibitory action of the 5-HT1A antagonist WAY-100635 on hippocampus pyramidal neurons. The function of terminal 5-HT1B autoreceptors was not changed as determined by the unaltered effectiveness of different frequencies of stimulation of the ascending 5-HT fibers. The function of α2-adrenergic receptors on 5-HT terminals was, however, diminished, as indicated by the lesser effect of the α2-adrenoceptor agonist clonidine. Tonic activation of postsynaptic α2- and α1-adrenoceptors by endogenous NE was also increased in 14-day bupropion-treated rats, as indicated by the greater effect of the α2- and α1-adrenoceptor antagonists idazoxan and prazosin, respectively, on pyramidal firing. The function of terminal α2-adrenergic autoreceptors was attenuated since increasing frequency of stimulation of the ascending NE pathway produced a lesser degree of suppression of pyramidal neurons in rats administered bupropion than the control.

Conclusion

Enhancement of 5-HT and NE transmissions in hippocampus by prolonged bupropion may account for its effectiveness in major depression.

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Abbreviations

5-HT:

5-Hydroxytryptamine

DR:

Dorsal raphe

LC:

Locus coeruleus

NE:

Norepinephrine

SSRI:

Selective serotonin reuptake inhibitor

WAY-100635:

N-{2-[4(2-methoxyphenyl)-1-piperazinyl] ethyl}-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride

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Acknowledgments

This research study was supported by the Canadian Institutes for Health Research grant (77838) to P. Blier, a Tier I Chair in Psychopharmacology from the Canadian Government, and an Endowed chair from the University of Ottawa Institute of Mental Health Research. P. Blier has received grants and/or honoraria from Astra Zeneca, Biovail, Bristol Myers Squibb, Eli Lilly, Janssen, Labopharm, Lundbeck/Takeda, Schering-Plough/Merck, Sepracor, Servier and Wyeth. R. Ghanbari and M. El Mansari have no conflict of interest.

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Authors and Affiliations

  1. Institute of Mental Health Research, University of Ottawa, Room 6411, 1145 Carling Avenue, Ottawa, K1Z 7K4, ON, Canada

    Ramez Ghanbari, Mostafa El Mansari & Pierre Blier

  2. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada

    Pierre Blier

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  1. Ramez Ghanbari
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  2. Mostafa El Mansari
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  3. Pierre Blier
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Correspondence to Pierre Blier.

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Ghanbari, R., El Mansari, M. & Blier, P. Enhancement of serotonergic and noradrenergic neurotransmission in the rat hippocampus by sustained administration of bupropion. Psychopharmacology 217, 61–73 (2011). https://doi.org/10.1007/s00213-011-2260-1

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  • DOI: https://doi.org/10.1007/s00213-011-2260-1

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