Acetylcholine nicotinic systems and serotonergic systems are known to interact. In rodents, acute and chronic nicotine treatments have consequences on several aspects of the activity of dorsal raphe serotonin (DRN 5-HT) neurons. One hypothesis is that states of functioning of DRN 5-HT neurons (firing rate and sensitivity) vary as a function of nicotine dose and mode of administration during chronic nicotine treatment. In the present study, the firing rate and sensitivity of DRN 5-HT neurons were investigated using single (0.5 and 1 mg/kg) or multiple (3 injections of 0.7 mg/kg) daily injections of nicotine over 10 days. The sensitivity of neurons was tested by the cumulative dose of the selective serotonin reuptake inhibitor citalopram necessary to inhibit their firing. The activity of neurons was tested during treatment, and then 24 and 48 h after nicotine withdrawal. The results show that, on day 10, DRN 5-HT neurons were desensitized (reduced response to citalopram) after chronic single daily injection treatments with the high dose of nicotine (1 mg/kg), while their sensitivity remained unaltered after single daily injections with the low dose (0.5 mg/kg), and after the multiple daily injection paradigm. None of the treatments altered the firing rate of DRN 5-HT neurons. The dose-dependent and time-dependent alterations of serotonergic neurons sensitivity after chronic nicotine treatments are likely the consequences of long-term adaptations of nicotinic receptors. The desensitization of DRN 5-HT neurons after chronic single daily injections of 1 mg/kg of nicotine suggests an antidepressant-like effect of chronic nicotine.
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http://dx.doi.org/10.1016/j.pbb.2008.01.005 | DOI Listing |
J Pharmacol Sci
February 2025
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan; Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, 565-0871, Japan; Project for Neural Networks, Drug Innovation Center, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, 565-0871, Japan. Electronic address:
Major depressive disorder (MDD) is among the most common mental disorders worldwide and is characterized by dysregulated reward processing associated with anhedonia. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for MDD; however, their onset of action is delayed. Recent reports have shown that serotonin neurons in the dorsal raphe nucleus (DRN) are activated by rewards and play a vital role in reward processing.
View Article and Find Full Text PDFBrain Struct Funct
December 2024
Laboratory of Molecular and Functional Neurobiology, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, SP, 05508-000, Brazil.
Serotonin (5-HT) is an important neurotransmitter for cognition and neurogenesis in the dentate gyrus (DG), which occurs via movement stimulation such as physical activity. Brain 5-HT function changes secondary to aging require further investigation. We evaluated whether aged animals would present changes in the number of 5-HT neurons in regions such as the dorsal (DRN) and median (MRN) raphe nuclei and possible changes in the rate of cellular activation in the DG in response to acute running, as a reduction in 5-HT neurons could contribute to a decline in neuronal activation in the DG in response to physical activity in aged mice.
View Article and Find Full Text PDFMetabolism
February 2025
USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
Obesity is a growing global health epidemic with limited orally administered therapeutics. Serotonin (5-HT) is one neurotransmitter which remains an excellent target for new weight-loss therapies, but a gap remains in understanding the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using an optogenetic feeding paradigm, we showed that the 5-HT➔arcuate nucleus (ARH) circuit plays a role in meal initiation.
View Article and Find Full Text PDFCNS Neurosci Ther
November 2024
Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Background: Dorsal raphe nucleus (DRN) serotonergic neurons projecting to the ventral tegmental area (VTA) neural circuit participate in regulating wake-related behaviors; however, the effect and mechanism of which in regulating sleep-wake are poorly understood.
Methods: Fiber photometry was used to study DRN serotonergic afferent activity changes in the VTA during sleep-wake processes. Optogenetics and chemogenetics were took advantage to study the effects of DRN serotonergic afferents modulating VTA during sleep-wake.
J Alzheimers Dis
January 2025
Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, USA.
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