title: Effects on serotonin of (-)nicotine and dimethylphenylpiperazinium in the dorsal raphe and nucleus accumbens of freely behaving rats.
abstract: The aim of this study was to investigate the neurochemical mechanism underlying the effect of nicotine and dimethylphenylpiperazinium (DMPP) on 5-hydroxytryptamine (5-HT) release in the dorsal raphe nucleus and nucleus accumbens of freely behaving rats. For comparison, lobeline, cytisine and RJR-2403 were also investigated. It was found that all drugs, when infused locally, evoked an increase of 5-HT in the dorsal raphe nucleus. However, the magnitudes of the 5-HT increase were comparatively different between the drugs in the ranking of their potency: DMPP>RJR 2403>>nicotine>lobeline>cytisine. Both methyllycaconitine, a nicotinic acetylcholine receptor (nAChR) antagonist and methyllycaconitine, a selective alpha7-containing nAChR antagonist blocked the effects of nicotine and DMPP, suggesting that alpha7 subunit mediated the increases in 5-HT. However, DMPP was reported to increase 5-HT using non-nAChR mechanism [Lendvai B, Sershen H, Lajtha A, Santha E, Baranyi M, Vizi ES (1996) Differential mechanisms involved in the effect of nicotinic agonists DMPP and lobeline to release [3H]5-HT from rat hippocampal slices. Neuropharmacology 35:1769-1777]. To test if 5-HT carriers were involved, a selective 5-HT reuptake inhibitor citalopram (1 microM) was infused into the dorsal raphe nucleus before administration of nicotine or DMPP. As a result, citalopram significantly blocked the effect of DMPP, whereas it had no influence on nicotine. Finally, the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was used to test whether the increases in 5-HT were depolarization-dependent. Administration of 8-OH-DPAT (0.1 mg/kg, s.c.) produced significant decreases in 5-HT in the animals treated with nicotine. In contrast, the effect of DMPP was not altered by 8-OH-DPAT, suggesting that the increases in 5-HT were independent of cell membrane depolarization. In conclusion, there are different mechanisms involved in nicotine- and DMPP-evoked increases in 5-HT. This is consistent with prior work suggesting DMPP may primarily act on 5-HT carriers.
authors.affiliation: Department of Biomedical Science, Charles E. Schmidt College of Science, Florida Atlantic University, 777 Glades Road, P.O. Box 3091, Boca Raton, FL 33431-0991, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Ma
authors.forename: R E
authors.initials: RE
authors.lastname: Strecker
authors.forename: J T
authors.initials: JT
authors.lastname: McKenna
authors.forename: M M
authors.initials: MM
authors.lastname: Thakkar
authors.forename: R W
authors.initials: RW
authors.lastname: McCarley
authors.forename: R
authors.initials: R
authors.lastname: Tao
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002352:Carrier Proteins; D015283:Citalopram; D004246:Dimethylphenylpiperazinium Iodide; D009538:Nicotine; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors