Flattening plasma corticosterone levels increases the prevalence of serotonergic dorsal raphe neurons inhibitory responses to nicotine in adrenalectomised rats

Highlights • Adrenalectomised and chronic corticosterone rats had flat corticosterone plasma levels. • In corticosterone treated rats, nicotine inhibited the firing of 5-HT dorsal raphe neurons. • In corticosterone treated rats nicotine and 5-HT increase IKIR. • Nicotine seems to induced 5-HT releas...

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Published inBrain research bulletin Vol. 98; pp. 10 - 22
Main Authors Frías-Domínguez, Carmen, Garduño, Julieta, Hernández, Salvador, Drucker-Colin, René, Mihailescu, Stefan
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.09.2013
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Abstract Highlights • Adrenalectomised and chronic corticosterone rats had flat corticosterone plasma levels. • In corticosterone treated rats, nicotine inhibited the firing of 5-HT dorsal raphe neurons. • In corticosterone treated rats nicotine and 5-HT increase IKIR. • Nicotine seems to induced 5-HT release in the dorsal raphe nucleus. • Nicotine effects are mediated by α4β2 nicotinic receptors.
AbstractList Major depression is characterized by a diminished activity of the brain serotonergic system as well as by the flattening of plasma cortisol levels. Nicotine improves mood in patients with major depression and in experimentally depressed animals by increasing brain serotonin (5-HT), noradrenaline and dopamine levels. The present study was directed to determine if flattening plasma glucocorticoid levels changes nicotine's stimulatory effects upon 5-HT DRN neurons. The experiments were performed in brain slices obtained from rats previously (14 days) adrenalectomised and implanted subcutaneously with one pellet containing 75mg of corticosterone (Adx+CSR rats). Whole cell voltage and current clamp techniques were used to study the activity of immunocitochemically identified 5-HT DRN neurons. Administration of nicotine (1μM) in sham-operated animals produced stimulatory effects in all 5-HT DRN neurons studied. In Adx+CSR rats however, nicotine inhibited 75% of 5-HT DRN neurons and increased the potassium-dependent inward rectifying current. The inhibitory effect of nicotine upon 5-HT DRN neurons was dependent on serotonin release inside the DRN, since it was converted into a stimulatory response by the selective antagonist of 5-HT1A receptors N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (WAY100635, 25nM). Adx+CSR rats also presented an increased function of 5-HT1A autoreceptors, since, in these rats, serotonin (1-10μM) produced a higher increase in the potassium dependent inward rectifying current in comparison with sham-operated animals. Serotonin release inside DRN was mediated by α4β2 nicotinic acetylcholine receptors since the selective antagonist of these receptors dihydro-β-erytroidine hydrobromide (DHβE, 100nM) blocked the inhibitory effects of nicotine 5-HT DRN neurons. These data indicate that, in the experimental model of adrenalectomised rats implanted with corticosterone pellets, nicotine increases the function of 5-HT1A receptors of 5-HT DRN neurons.
•Adrenalectomised and chronic corticosterone rats had flat corticosterone plasma levels.•In corticosterone treated rats, nicotine inhibited the firing of 5-HT dorsal raphe neurons.•In corticosterone treated rats nicotine and 5-HT increase IKIR.•Nicotine seems to induced 5-HT release in the dorsal raphe nucleus.•Nicotine effects are mediated by α4β2 nicotinic receptors. Major depression is characterized by a diminished activity of the brain serotonergic system as well as by the flattening of plasma cortisol levels. Nicotine improves mood in patients with major depression and in experimentally depressed animals by increasing brain serotonin (5-HT), noradrenaline and dopamine levels. The present study was directed to determine if flattening plasma glucocorticoid levels changes nicotine's stimulatory effects upon 5-HT DRN neurons. The experiments were performed in brain slices obtained from rats previously (14 days) adrenalectomised and implanted subcutaneously with one pellet containing 75mg of corticosterone (Adx+CSR rats). Whole cell voltage and current clamp techniques were used to study the activity of immunocitochemically identified 5-HT DRN neurons. Administration of nicotine (1μM) in sham-operated animals produced stimulatory effects in all 5-HT DRN neurons studied. In Adx+CSR rats however, nicotine inhibited 75% of 5-HT DRN neurons and increased the potassium-dependent inward rectifying current. The inhibitory effect of nicotine upon 5-HT DRN neurons was dependent on serotonin release inside the DRN, since it was converted into a stimulatory response by the selective antagonist of 5-HT1A receptors N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (WAY100635, 25nM). Adx+CSR rats also presented an increased function of 5-HT1A autoreceptors, since, in these rats, serotonin (1–10μM) produced a higher increase in the potassium dependent inward rectifying current in comparison with sham-operated animals. Serotonin release inside DRN was mediated by α4β2 nicotinic acetylcholine receptors since the selective antagonist of these receptors dihydro-β-erytroidine hydrobromide (DHβE, 100nM) blocked the inhibitory effects of nicotine 5-HT DRN neurons. These data indicate that, in the experimental model of adrenalectomised rats implanted with corticosterone pellets, nicotine increases the function of 5-HT1A receptors of 5-HT DRN neurons.
Highlights • Adrenalectomised and chronic corticosterone rats had flat corticosterone plasma levels. • In corticosterone treated rats, nicotine inhibited the firing of 5-HT dorsal raphe neurons. • In corticosterone treated rats nicotine and 5-HT increase IKIR. • Nicotine seems to induced 5-HT release in the dorsal raphe nucleus. • Nicotine effects are mediated by α4β2 nicotinic receptors.
Author Garduño, Julieta
Drucker-Colin, René
Hernández, Salvador
Mihailescu, Stefan
Frías-Domínguez, Carmen
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CitedBy_id crossref_primary_10_1152_jn_00223_2014
crossref_primary_10_1515_revneuro_2018_0014
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Keywords nAChRs
DRN
Serotonin
Adx + CSR rats
Corticosterone
Dorsal raphe nucleus
adrenalectomised and corticosterone-treated rats
nicotinic acetylcholine receptors
5-HT1A receptor
Nicotine
Adx+CSR rats
Language English
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Snippet Highlights • Adrenalectomised and chronic corticosterone rats had flat corticosterone plasma levels. • In corticosterone treated rats, nicotine inhibited the...
•Adrenalectomised and chronic corticosterone rats had flat corticosterone plasma levels.•In corticosterone treated rats, nicotine inhibited the firing of 5-HT...
Major depression is characterized by a diminished activity of the brain serotonergic system as well as by the flattening of plasma cortisol levels. Nicotine...
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StartPage 10
SubjectTerms 5-HT1A receptor
Aconitine - analogs & derivatives
Aconitine - pharmacology
Action Potentials - drug effects
Adrenalectomy
Animals
Corticosterone
Corticosterone - blood
Dihydro-beta-Erythroidine - pharmacology
Dorsal raphe nucleus
Dose-Response Relationship, Drug
Male
Neural Inhibition - drug effects
Neurology
Nicotine
Nicotine - pharmacology
Nicotinic Agonists - pharmacology
Nicotinic Antagonists - pharmacology
Piperazines - pharmacology
Pyridines - pharmacology
Raphe Nuclei - cytology
Raphe Nuclei - drug effects
Rats
Rats, Wistar
Serotonergic Neurons - drug effects
Serotonin
Serotonin - metabolism
Serotonin - pharmacology
Serotonin Antagonists - pharmacology
Title Flattening plasma corticosterone levels increases the prevalence of serotonergic dorsal raphe neurons inhibitory responses to nicotine in adrenalectomised rats
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https://dx.doi.org/10.1016/j.brainresbull.2013.07.006
https://www.ncbi.nlm.nih.gov/pubmed/23872451
https://search.proquest.com/docview/1444393834
Volume 98
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