Expression data from the Lateral Habenula (LHb) and the Medial Habenula (MHb) of the mouse (C57BL/6) brain after nicotine self-administration
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ABSTRACT:
ORGANISM(S): synthetic construct Mus musculus
PROVIDER: GSE66453 | GEO | 2015/03/04
SECONDARY ACCESSION(S): PRJNA277003
REPOSITORIES: GEO
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Project description:After intarvenouse catheter surgery, nicotine self-administration using an operant self-administration chamber, was conducted for 44 days with various doses of nicotine solution. Age-matched mice were used for control. After the self-administration, the Lateral Habenual (LHb) and the Medial Habenula (MHb) of the mouse brain were collected. We used microarrays to detail the mRNA expression profile of the Lateral Habenual (LHb) and the Medial Habenula (MHb) after the nicotine self-administration.
2015-03-04 | E-GEOD-66451 | biostudies-arrayexpress
Project description:After intarvenouse catheter surgery, nicotine self-administration using an operant self-administration chamber, was conducted for 44 days with various doses of nicotine solution. Age-matched mice were used for control. After the self-administration, the Lateral Habenual (LHb) and the Medial Habenula (MHb) of the mouse brain were collected.
2015-03-04 | GSE66452 | GEO
Project description:After intarvenouse catheter surgery, nicotine self-administration using an operant self-administration chamber, was conducted for 44 days with various doses of nicotine solution. Age-matched mice were used for control. After the self-administration, the Lateral Habenual (LHb) and the Medial Habenula (MHb) of the mouse brain were collected.
2015-03-04 | GSE66451 | GEO
Project description:The CYP2B enzyme is expressed in human and rat brain, and metabolizes many CNS-acting drugs. The gene that encodes human CYP2B6 is highly polymorphic, where the variation in brain enzyme levels could result in altered brain drug levels. CYP2B can metabolize nicotine, the main psychoactive ingredient in cigarettes; if altered brain CYP2B activity can influence nicotine brain levels, it could influence nicotine-mediated behaviors. To investigate this, a mechanism-based inhibitor selective for CYP2B, C8-xanthate (20 ?g), was administered intracerebroventricularly (ICV) into the brain of rats, and 22 h later, nicotine levels were measured by in vivo microdialysis following nicotine (150 ?g/kg intravenous). Brain nicotine levels from 15 to 30 min and the AUC0-45 min were both twofold higher (p<0.05) with C8-xanthate vs vehicle pretreatment; there was no difference in peripheral nicotine levels. Rats were then given ICV pretreatment with C8-xanthate/ASCF and underwent intravenous nicotine self-administration with 3.75-30 ?g/kg per infusion dose. C8-xanthate pretreatment increased responding in progressive ratio (15 ?g/kg per infusion dose, p<0.05). In a separate cohort, C8-xanthate increased the percentage of rats that acquired self-administration (7.5 ?g/kg per infusion dose, p<0.05) from 40% after vehicle pretreatment to 100%, with no difference in peripheral nicotine levels measured at the end of behavior. In a third cohort, C8-xanthate increased the number of sessions required to meet extinction criteria (p<0.05). Together these data demonstrate that the brain CYP2B activity can influence nicotine brain levels and subsequent behaviors independent of hepatic metabolism. This suggests that human smokers with variable CYP2B brain levels could have different nicotine levels and reinforcement, which might have a role in smoking behaviors and dependence.
| S-EPMC4839514 | biostudies-other
Project description:Intrinsic daily or circadian rhythms arise through the outputs of the master circadian clock in the brain's suprachiasmatic nuclei (SCN) as well as circadian oscillators in other brain sites and peripheral tissues. SCN neurones contain an intracellular molecular clock that drives these neurones to exhibit pronounced day-night differences in their electrical properties. The epithalamic medial habenula (MHb) expresses clock genes, but little is known about the bioelectric properties of mouse MHb neurones and their potential circadian characteristics. Therefore, in this study we used a brain slice preparation containing the MHb to determine the basic electrical properties of mouse MHb neurones with whole-cell patch clamp electrophysiology, and investigated whether these vary across the day-night cycle. MHb neurones (n = 230) showed heterogeneity in electrophysiological state, ranging from highly depolarised cells (∼ -25 to -30 mV) that are silent with no membrane activity or display depolarised low-amplitude membrane oscillations, to neurones that were moderately hyperpolarised (∼40 mV) and spontaneously discharging action potentials. These electrical states were largely intrinsically regulated and were influenced by the activation of small-conductance calcium-activated potassium channels. When considered as one population, MHb neurones showed significant circadian variation in their spontaneous firing rate and resting membrane potential. However, in recordings of MHb neurones from mice lacking the core molecular circadian clock, these temporal differences in MHb activity were absent, indicating that circadian clock signals actively regulate the timing of MHb neuronal states. These observations add to the extracellularly recorded rhythms seen in other brain areas and establish that circadian mechanisms can influence the membrane properties of neurones in extra-SCN sites. Collectively, the results of this study indicate that the MHb may function as an intrinsic secondary circadian oscillator in the brain, which can shape daily information flow in key brain processes, such as reward and addiction.
| S-EPMC3934703 | biostudies-literature
Project description:RationaleTesting genetically engineered mice in a reliable nicotine self-administration procedure could provide important insights into the molecular mechanisms underlying nicotine reinforcement.ObjectivesWe assessed operant responding for intravenous nicotine infusions in C57BL/6J male mice under a fixed-ratio 3 schedule of reinforcement in which a visual cue was contingently associated with drug delivery.Methods/resultsAcquisition, dose-response function, extinction, and cue-induced reinstatement of operant behavior were characterized. Low nicotine doses (0.001-0.06 mg/kg/infusion) elicited response rates similar to those supported by saline, whereas a higher dose (0.1 mg/kg/infusion) decreased responding. Using an identical procedure to assess cocaine self-administration in an independent group of mice yielded an inverted U-shaped dose-response curve. Other mice trained to respond exclusively for the visual stimulus earned a similar number of reinforcers as mice self-administering saline or low nicotine doses, although with a lower selectivity for the active lever and their response rates were sensitive to the discontinuation and resumption of cue light presentation. Finally, patterns of responding for nicotine, cocaine, or the visual stimulus alone were analyzed using frequency distributions of inter-response intervals and extended return maps. These analyses revealed unique properties of nicotine, which dose-dependently delayed the first response post-timeout and increased the regularity of lever pressing activity.ConclusionsNicotine did not enhance the reinforcing properties of the visual cue paired with drug delivery. Interestingly, however, patterns of responding could differentiate nicotine self-administration from responding for a visual stimulus or saline and indicated that nicotine functioned as a salient stimulus driving highly regular operant behavior.
| S-EPMC2952765 | biostudies-literature
Project description:Serotonin (5-HT) is important in some nicotine actions in the CNS. Among all the 5-HT receptors (5-HTRs), the 5-HT2CR has emerged as a promising drug target for smoking cessation. The 5-HT2CRs within the lateral habenula (LHb) may be crucial for nicotine addiction. Here we showed that after acute nicotine tartrate (2 mg/kg, i.p.) exposure, the 5-HT2CR agonist Ro 60-0175 (5-640 µg/kg, i.v.) increased the electrical activity of 42% of the LHb recorded neurons in vivo in rats. Conversely, after chronic nicotine treatment (6 mg/kg/day, i.p., for 14 days), Ro 60-0175 was incapable of affecting the LHb neuronal discharge. Moreover, acute nicotine exposure increased the 5-HT2CR-immunoreactive (IR) area while decreasing the number of 5-HT2CR-IR neurons in the LHb. On the other hand, chronic nicotine increased both the 5-HT2CR-IR area and 5-HT2CR-IR LHb neurons in the LHb. Western blot analysis confirmed these findings and further revealed an increase of 5-HT2CR expression in the medial prefrontal cortex after chronic nicotine exposure not detected by the immunohistochemistry. Altogether, these data show that acute and chronic nicotine exposure differentially affect the central 5-HT2CR function mainly in the LHb and this may be relevant in nicotine addiction and its treatment.
| S-EPMC8124296 | biostudies-literature
Project description:The medial habenula (MHb) plays an important role in nicotine-related behaviors, such as aversion and withdrawal. The MHb is composed of distinct subregions with unique neurotransmitter expression and neuronal connectivity. Here, we showed that nicotine and substance P (SP) differentially regulate neuronal excitability in subdivisions of the MHb (ventrolateral division, MHbVL; dorsal division; MHbD and superior division: MHbS). Nicotine remarkably increased spontaneous neuronal firing in the MHbVL and MHbD, but not in the MHbS, which was consistent with different magnitudes of whole-cell inward currents evoked by nicotine in each subdivision. Meanwhile, SP enhanced neuronal excitability in the MHbVL and MHbS. Although the MHbD is composed of SP-expressing neurons, they did not respond to SP. Neurons in the MHbVL increased their firing in response to bath-applied nicotine, which was attenuated by neurokinin receptor antagonists. Furthermore, nicotine addiction and withdrawal attenuated and augmented excitatory SP effects in the MHbVL, respectively. On the whole, we suggest that MHb-involving nicotine-related behaviors might be associated with SP signaling in MHb subdivisions.
| S-EPMC6138320 | biostudies-other
Project description:Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, has been investigated for treatment of substance abuse-related disorders. Smoking cessation has major benefits for both individuals and society, therefore the aim of this study was to evaluate the potential of noribogaine for use as a treatment for nicotine dependence. Adult male Sprague-Dawley rats were trained to self-administer nicotine intravenous. After initial food pellet training, followed by 26 sessions of nicotine self-administration training, the rats were administered noribogaine (12.5, 25 or 50 mg/kg orally), noribogaine vehicle, varenicline or saline using a within-subject design with a Latin square test schedule. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% of saline-treated rats' levels and was equi-effective to 1.7 mg/kg intraperitoneal varenicline. Noribogaine was less efficient at reducing food pellets self-administration than at nicotine self-administration, inhibiting the nondrug reinforcing effects of palatable pellets by 23% at the highest dose. These results suggest that noribogaine dose-dependently attenuates drug-taking behavior for nicotine, attenuates the reinforcing effects of nicotine and is comparable to varenicline power in that regard. The findings from the present study hold promise for a new therapy to aid smoking cessation.
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Project description:Treatment-resistant depression (TRD) is a chronic and severe psychiatric illness associated with limited therapeutic options. Deep brain stimulation (DBS) is a promising therapy for TRD patients. However, its safety and efficacy are still unclear. Here we reported the safety and efficacy of lateral habenula (LHb) DBS for a TRD patient who had failed medical, psychological, electroconvulsive, and ketamine therapy. The DBS system is compatible with 3T magnetic resonance imaging along with local field potential (LFP) streaming. Two DBS electrodes were implanted at the bilateral LHb without any complication. The patient showed acute stimulation effects and achieved long-term improvements in his depression, anxiety, and sleep with left LHb 160 Hz frequency stimulation, accompanying the change of LFPs. These results provided clinical evidence toward the safety and efficacy and electrophysiological basis of LHb DBS for TRD.
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