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Chronic oral nicotine increases brain [3H]epibatidine binding and responsiveness to antidepressant drugs, but not nicotine, in the mouse forced swim test.

Abstract：

INTRODUCTION:Smoking rates among depressed individuals is higher than among healthy subjects, and nicotine alleviates depressive symptoms. Nicotine increases serotonergic and noradrenergic neuronal activity and facilitates serotonin and noradrenaline release. In mice, acute nicotine administration enhances the activity of antidepressants in the mouse forced swim (mFST) and tail suspension tests. Here, we investigated if this action of nicotine is also reflected in a chronic treatment regimen. MATERIALS AND METHODS:After chronic treatment with nicotine in the drinking water, mice were challenged with nicotine, duloxetine, citalopram, and reboxetine in the mFST. Additionally, 8-OH-DPAT- and clonidine-induced hypothermia was tested in vehicle- and nicotine-pretreated mice, as a measure of 5-HT(1A) and alpha(2)-adrenoceptor function, respectively. Finally, the effects on the brain expression levels of high- and low-affinity nicotinic acetylcholine receptors (nAChRs) and the transporters for serotonin (SERT) and noradrenaline (NET) were assessed using [(3)H]epibatidine, [(3)H]alpha-bungarotoxin, [(3)H]citalopram, and [(3)H]nisoxetine binding, respectively. RESULTS:In the mFST, nicotine-pretreated mice did not show altered response to the nicotine challenge, but increased responses to all three antidepressants tested were observed when compared to mice that had been administered drinking water without nicotine. There was no change in hypothermic responses to 8-OH-DPAT or clonidine. [(3)H]epibatidine binding was significantly increased in all brain regions investigated; whereas, [(3)H]alpha-bungarotoxin, [(3)H]citalopram, and [(3)H]nisoxetine binding were not altered, indicating that chronic oral nicotine increases the expression and/or affinity of high-affinity nAChRs, but not low-affinity nAChRs, SERT, or NET. DISCUSSION:It is suggested that the increased sensitivity to antidepressants after chronic nicotine exposure involves increased high-affinity nAChR-mediated neurotransmission.

journal_name

Psychopharmacology (Berl)

journal_title

Psychopharmacology

authors

Andreasen JT,Nielsen EO,Redrobe JP

doi

10.1007/s00213-009-1560-1

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

517-28

issue

eissn

0033-3158

issn

1432-2072

journal_volume

205

pub_type

杂志文章

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Chronic oral nicotine increases brain [3H]epibatidine binding and responsiveness to antidepressant drugs, but not nicotine, in the mouse forced swim test.