title: Flattening plasma corticosterone levels increases the prevalence of serotonergic dorsal raphe neurons inhibitory responses to nicotine in adrenalectomised rats.
abstract: 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.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México DF, Mexico.
authors.forename: Carmen
authors.initials: C
authors.lastname: Frías-Domínguez
authors.forename: Julieta
authors.initials: J
authors.lastname: Garduño
authors.forename: Salvador
authors.initials: S
authors.lastname: Hernández
authors.forename: René
authors.initials: R
authors.lastname: Drucker-Colin
authors.forename: Stefan
authors.initials: S
authors.lastname: Mihailescu
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000097:blood*; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D059326:Serotonergic Neurons / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D012701:Serotonin; D009538:Nicotine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D003345:Corticosterone; D000157:Aconitine
keywords: 5-HT1A receptor; Adx+CSR rats; Corticosterone; DRN; Dorsal raphe nucleus; Nicotine; Serotonin; adrenalectomised and corticosterone-treated rats; dorsal raphe nucleus; nAChRs; nicotinic acetylcholine receptors