Abstract:
:Ibogaine, an alkaloid extracted from Tabemanthe iboga, is being studied as a potential long-acting treatment for oploid and stimulant abuse as well as for alcoholism and smoking. Studies in this laboratory have used animal models to characterize ibogaine's interactions with drugs of abuse, and to investigate the mechanisms responsible. Ibogaine, as well as its metabolite, noribogaine, can decrease both morphine and cocaine self-administration for several days in some rats; shorter-lasting effects appear to occur on ethanol and nicotine intake. Acutely, both ibogaine and noribogaine decrease extracellular levels of dopamine in the nucleus accumbens of rat brain. Ibogaine pretreatment (19 hours beforehand) blocks morphine-induced dopamine release and morphine-induced locomotor hyperactivity while, in contrast, it enhances similar effects of stimulants (cocaine and amphetamine). Ibogaine pretreatment also blocks nicotine-induced dopamine release. Both ibogaine and noribogaine bind to kappa opioid and N-methyl-D-aspartate (NMDA) receptors and to serotonin uptake sites; ibogaine also binds to sigma-2 and nicotinic receptors. The relative contributions of these actions are being assessed. Our ongoing studies in rats suggest that kappa agonist and NMDA antagonist actions contribute to ibogaine's effects on opioid and stimulant self-administration, while the serotonergic actions may be more important for ibogaine-induced decreases in alcohol intake. A nicotinic antagonist action may mediate ibogaine-induced reduction of nicotine preferences in rats. A sigma-2 action of ibogaine appears to mediate its neurotoxicity. Some effects of ibogaine (e.g., on morphine and cocaine self-administration, morphine-induced hyperactivity, cocaine-induced increases in nucleus accumbens dopamine) are mimicked by kappa agonist (U50,488) and/or a NMDA antagonist (MK-801). Moreover, a combination of a kappa antagonist and a NMDA agonist will partially reverse several of ibogaine's effects. Ibogaine's long-term effects may be mediated by slow release from fat tissue (where ibogaine is sequestered) and conversion to noribogaine. Different receptors, or combinations of receptors, may mediate interactions of ibogaine with different drugs of abuse.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Glick SD,Maisonneuve ISsubject
Has Abstractpub_date
1998-05-30 00:00:00pages
214-26eissn
0077-8923issn
1749-6632journal_volume
844pub_type
杂志文章,评审abstract::After a complete spinal cord injury (SCI) at the lowest thoracic level (T13), adult cats trained to walk on a treadmill can recover hindlimb locomotion within 2-3 weeks, resulting from the activity of a spinal circuitry termed the central pattern generator (CPG). The role of this spinal circuitry in the recovery of lo...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
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abstract::T cell protein tyrosine phosphatase (TCPTP) dephosphorylates a number of substrates, including JAK-STAT (signal transducer and activator of transcription) signaling proteins, which are activated by interferon (IFN)-γ, a major proinflammatory cytokine involved in conditions such as inflammatory bowel disease. A critica...
journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
pub_type: 评论,杂志文章,评审
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
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journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
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abstract::Many risk factors have been identified as having either a protective or a negative effect on the development of fibroids, but due to methodological issues and a lack of long-term studies, the exact effect of these factors is ambiguous. In similar dispute is the proper treatment of fibroids. Recent technological advanc...
journal_title:Annals of the New York Academy of Sciences
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abstract::Lesion, stimulation, and pharmacological studies point to separate hypothalamic control of pulsatile FSH and LH secretion. LH release is controlled by a region extending from the preoptic area to the anterior and mid-median eminence, whereas FSH release is controlled by a region extending from the dorsal anterior hypo...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
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journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
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journal_title:Annals of the New York Academy of Sciences
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abstract::Managed care organizations and their affiliated group practices approach technology evaluation in a methodical way. This paper reviews the factors used in analysis of ultrasound for the diagnosis of fetal anomalies. It includes one group practice's strategies for ultrasound management while supporting the use of the s...
journal_title:Annals of the New York Academy of Sciences
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abstract::One of the most remarkable aspects of the immune system is its ability to fashion an immune response most appropriate to the activating stimulus. Although the immune system possesses a number of adaptations to accomplish this, an important theme is local immune regulation by site-specific expression of receptors and l...
journal_title:Annals of the New York Academy of Sciences
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abstract::Epidemiological observations, clinical mechanistic studies, and basic laboratory research suggest that estrogen therapy is associated with beneficial cardiovascular effects in postmenopausal women. Estrogen has a multitude of biological effects that may account for this apparent benefit (which remains to be proved in ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
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更新日期:2001-12-01 00:00:00
abstract::Red spruce (Picea rubens Sarg.) and balsam fir (Abies balsamea (L.) Mill.) were present by 13,700 years B.C.E. in the Catskills Mountains of southeastern New York State. These conifers were, and still are, largely confined to the eastern and far western portions of the region. A gap in the distribution exists between ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
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更新日期:2013-09-01 00:00:00