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Gioacchino Calapai - One of the best experts on this subject based on the ideXlab platform.
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Hypericum perforatum attenuates nicotine withdrawal signs in mice
Psychopharmacology, 2003Co-Authors: Maria A. Catania, Fabio Firenzuoli, Anna Crupi, Carmen Mannucci, Achille P. Caputi, Gioacchino CalapaiAbstract:Rationale Hypericum perforatum is used as a natural antidepressant, and other antidepressants have been marketed to aid in smoking cessation. Objective We investigated the effects of an extract of Hypericum perforatum (Ph-50) on withdrawal signs produced by nicotine abstinence in mice. Methods Nicotine (2 mg/kg, four injections daily) was administered for 14 days to mice. Different doses of Ph-50 (125–500 mg/kg) were administered orally immediately after the last nicotine injection. In another experiment, Ph-50 (500 mg/kg) was orally administered in combination with nicotine, i) starting from day 8 until the end of the nicotine treatment period, or ii) during nicotine treatment and after nicotine withdrawal, or iii) immediately after the last nicotine injection. On withdrawal from nicotine, all animals were evaluated for locomotor activity and abstinence signs. Results The locomotor activity reduction induced by nicotine withdrawal was abolished by Ph-50, which also significantly and dose-dependently reduced the total nicotine abstinence score when injected after nicotine withdrawal. Conclusions These data show that treatment with Hypericum perforatum attenuates nicotine withdrawal signs in mice. Further studies are necessary to test the possibility that it may be used for smoking cessation treatment in humans.
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Hypericum perforatum attenuates nicotine withdrawal signs in mice.
Psychopharmacology, 2003Co-Authors: Maria A. Catania, Fabio Firenzuoli, Anna Crupi, Carmen Mannucci, Achille P. Caputi, Gioacchino CalapaiAbstract:Hypericum perforatum is used as a natural antidepressant, and other antidepressants have been marketed to aid in smoking cessation. We investigated the effects of an extract of Hypericum perforatum (Ph-50) on withdrawal signs produced by nicotine abstinence in mice. Nicotine (2 mg/kg, four injections daily) was administered for 14 days to mice. Different doses of Ph-50 (125–500 mg/kg) were administered orally immediately after the last nicotine injection. In another experiment, Ph-50 (500 mg/kg) was orally administered in combination with nicotine, i) starting from day 8 until the end of the nicotine treatment period, or ii) during nicotine treatment and after nicotine withdrawal, or iii) immediately after the last nicotine injection. On withdrawal from nicotine, all animals were evaluated for locomotor activity and abstinence signs. The locomotor activity reduction induced by nicotine withdrawal was abolished by Ph-50, which also significantly and dose-dependently reduced the total nicotine abstinence score when injected after nicotine withdrawal. These data show that treatment with Hypericum perforatum attenuates nicotine withdrawal signs in mice. Further studies are necessary to test the possibility that it may be used for smoking cessation treatment in humans.
Fernando B De Moura - One of the best experts on this subject based on the ideXlab platform.
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unexpected loss of sensitivity to the nicotinic acetylcholine receptor antagonist activity of mecamylamine and dihydro β erythroidine in nicotine tolerant mice
Brain and behavior, 2020Co-Authors: Fernando B De Moura, Jenny L Wilkerson, Lance R McmahonAbstract:OBJECTIVES There is a long-standing interest in developing nicotinic acetylcholine receptor (nAChR) antagonists for concomitant use with nAChR agonists (e.g., nicotine replacement) as complementary smoking cessation aids. Previous studies demonstrate that daily nicotine treatment confers tolerance to some effects of nicotine, as well as cross-tolerance to other nAChR agonists. The current study assessed the extent to which antagonism of nicotine varies as a function of daily nicotine treatment. METHODS Schedule-controlled responding and hypothermia were selected for study because they have been previously used to examine the pharmacology of nicotine, and both are sensitive to the development nicotine tolerance. The rate-decreasing and hypothermic effects of nicotine, as well as antagonism of those effects, were examined in C57BL/6J mice before, during treatment with, and after discontinuation of three daily injections of 1.78 mg/kg nicotine. The nonselective nAChR antagonist mecamylamine and the β2 nAChR antagonist dihydro-β-erythroidine (DHβE) were studied in combination with nicotine. RESULTS The ED50 values of nicotine to produce rate-decreasing and hypothermic effects were, respectively, 0.44 and 0.82 mg/kg prior, 1.6 and 3.2 mg/kg during, and 0.74 and 1.1 mg/kg after discontinuation of daily nicotine treatment. Prior to daily nicotine treatment, mecamylamine decreased response rate and rectal temperature. However, during daily nicotine, mecamylamine (up to 5.6 mg/kg) only decreased rectal temperature. DHβE (up to 5.6 mg/kg) when studied prior to daily nicotine decreased rectal temperature, but that decrease was abolished during chronic nicotine treatment. Mecamylamine and DHβE antagonized the rate-decreasing and hypothermic effects of nicotine before and after daily nicotine; however, during daily nicotine, mecamylamine and DHβE antagonized only the hypothermic effects of nicotine. CONCLUSIONS The differential antagonism of rate-decreasing and hypothermic effects implicates differential involvement of nAChR subtypes. The decreased capacity of mecamylamine and DHβE to antagonize nicotine during chronic nicotine treatment may indicate that their effectiveness as smoking cessations might vary as a function of nicotine tolerance and dependence.
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unexpected loss of sensitivity to the nicotinic acetylcholine receptor antagonist activity of mecamylamine and dihydro β erythroidine in nicotine tolerant mice
Brain and behavior, 2020Co-Authors: Fernando B De Moura, Jenny L Wilkerson, Lance R McmahonAbstract:OBJECTIVES: There is a long-standing interest in developing nicotinic acetylcholine receptor (nAChR) antagonists for concomitant use with nAChR agonists (e.g., nicotine replacement) as complementary smoking cessation aids. Previous studies demonstrate that daily nicotine treatment confers tolerance to some effects of nicotine, as well as cross-tolerance to other nAChR agonists. The current study assessed the extent to which antagonism of nicotine varies as a function of daily nicotine treatment. METHODS: Schedule-controlled responding and hypothermia were selected for study because they have been previously used to examine the pharmacology of nicotine, and both are sensitive to the development nicotine tolerance. The rate-decreasing and hypothermic effects of nicotine, as well as antagonism of those effects, were examined in C57BL/6J mice before, during treatment with, and after discontinuation of three daily injections of 1.78 mg/kg nicotine. The nonselective nAChR antagonist mecamylamine and the beta2 nAChR antagonist dihydro-beta-erythroidine (DHbetaE) were studied in combination with nicotine. RESULTS: The ED50 values of nicotine to produce rate-decreasing and hypothermic effects were, respectively, 0.44 and 0.82 mg/kg prior, 1.6 and 3.2 mg/kg during, and 0.74 and 1.1 mg/kg after discontinuation of daily nicotine treatment. Prior to daily nicotine treatment, mecamylamine decreased response rate and rectal temperature. However, during daily nicotine, mecamylamine (up to 5.6 mg/kg) only decreased rectal temperature. DHbetaE (up to 5.6 mg/kg) when studied prior to daily nicotine decreased rectal temperature, but that decrease was abolished during chronic nicotine treatment. Mecamylamine and DHbetaE antagonized the rate-decreasing and hypothermic effects of nicotine before and after daily nicotine; however, during daily nicotine, mecamylamine and DHbetaE antagonized only the hypothermic effects of nicotine. CONCLUSIONS: The differential antagonism of rate-decreasing and hypothermic effects implicates differential involvement of nAChR subtypes. The decreased capacity of mecamylamine and DHbetaE to antagonize nicotine during chronic nicotine treatment may indicate that their effectiveness as smoking cessations might vary as a function of nicotine tolerance and dependence.
Lance R Mcmahon - One of the best experts on this subject based on the ideXlab platform.
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unexpected loss of sensitivity to the nicotinic acetylcholine receptor antagonist activity of mecamylamine and dihydro β erythroidine in nicotine tolerant mice
Brain and behavior, 2020Co-Authors: Fernando B De Moura, Jenny L Wilkerson, Lance R McmahonAbstract:OBJECTIVES There is a long-standing interest in developing nicotinic acetylcholine receptor (nAChR) antagonists for concomitant use with nAChR agonists (e.g., nicotine replacement) as complementary smoking cessation aids. Previous studies demonstrate that daily nicotine treatment confers tolerance to some effects of nicotine, as well as cross-tolerance to other nAChR agonists. The current study assessed the extent to which antagonism of nicotine varies as a function of daily nicotine treatment. METHODS Schedule-controlled responding and hypothermia were selected for study because they have been previously used to examine the pharmacology of nicotine, and both are sensitive to the development nicotine tolerance. The rate-decreasing and hypothermic effects of nicotine, as well as antagonism of those effects, were examined in C57BL/6J mice before, during treatment with, and after discontinuation of three daily injections of 1.78 mg/kg nicotine. The nonselective nAChR antagonist mecamylamine and the β2 nAChR antagonist dihydro-β-erythroidine (DHβE) were studied in combination with nicotine. RESULTS The ED50 values of nicotine to produce rate-decreasing and hypothermic effects were, respectively, 0.44 and 0.82 mg/kg prior, 1.6 and 3.2 mg/kg during, and 0.74 and 1.1 mg/kg after discontinuation of daily nicotine treatment. Prior to daily nicotine treatment, mecamylamine decreased response rate and rectal temperature. However, during daily nicotine, mecamylamine (up to 5.6 mg/kg) only decreased rectal temperature. DHβE (up to 5.6 mg/kg) when studied prior to daily nicotine decreased rectal temperature, but that decrease was abolished during chronic nicotine treatment. Mecamylamine and DHβE antagonized the rate-decreasing and hypothermic effects of nicotine before and after daily nicotine; however, during daily nicotine, mecamylamine and DHβE antagonized only the hypothermic effects of nicotine. CONCLUSIONS The differential antagonism of rate-decreasing and hypothermic effects implicates differential involvement of nAChR subtypes. The decreased capacity of mecamylamine and DHβE to antagonize nicotine during chronic nicotine treatment may indicate that their effectiveness as smoking cessations might vary as a function of nicotine tolerance and dependence.
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unexpected loss of sensitivity to the nicotinic acetylcholine receptor antagonist activity of mecamylamine and dihydro β erythroidine in nicotine tolerant mice
Brain and behavior, 2020Co-Authors: Fernando B De Moura, Jenny L Wilkerson, Lance R McmahonAbstract:OBJECTIVES: There is a long-standing interest in developing nicotinic acetylcholine receptor (nAChR) antagonists for concomitant use with nAChR agonists (e.g., nicotine replacement) as complementary smoking cessation aids. Previous studies demonstrate that daily nicotine treatment confers tolerance to some effects of nicotine, as well as cross-tolerance to other nAChR agonists. The current study assessed the extent to which antagonism of nicotine varies as a function of daily nicotine treatment. METHODS: Schedule-controlled responding and hypothermia were selected for study because they have been previously used to examine the pharmacology of nicotine, and both are sensitive to the development nicotine tolerance. The rate-decreasing and hypothermic effects of nicotine, as well as antagonism of those effects, were examined in C57BL/6J mice before, during treatment with, and after discontinuation of three daily injections of 1.78 mg/kg nicotine. The nonselective nAChR antagonist mecamylamine and the beta2 nAChR antagonist dihydro-beta-erythroidine (DHbetaE) were studied in combination with nicotine. RESULTS: The ED50 values of nicotine to produce rate-decreasing and hypothermic effects were, respectively, 0.44 and 0.82 mg/kg prior, 1.6 and 3.2 mg/kg during, and 0.74 and 1.1 mg/kg after discontinuation of daily nicotine treatment. Prior to daily nicotine treatment, mecamylamine decreased response rate and rectal temperature. However, during daily nicotine, mecamylamine (up to 5.6 mg/kg) only decreased rectal temperature. DHbetaE (up to 5.6 mg/kg) when studied prior to daily nicotine decreased rectal temperature, but that decrease was abolished during chronic nicotine treatment. Mecamylamine and DHbetaE antagonized the rate-decreasing and hypothermic effects of nicotine before and after daily nicotine; however, during daily nicotine, mecamylamine and DHbetaE antagonized only the hypothermic effects of nicotine. CONCLUSIONS: The differential antagonism of rate-decreasing and hypothermic effects implicates differential involvement of nAChR subtypes. The decreased capacity of mecamylamine and DHbetaE to antagonize nicotine during chronic nicotine treatment may indicate that their effectiveness as smoking cessations might vary as a function of nicotine tolerance and dependence.
Hanan Frenk - One of the best experts on this subject based on the ideXlab platform.
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Reevaluating the nicotine delivery kinetics hypothesis
Psychopharmacology, 2007Co-Authors: Hanan FrenkAbstract:Rationale The view of smoking as an addiction to nicotine implies that nicotine is an addictive drug and a primary reinforcer. However, nicotine other than in tobacco does not appear to be very rewarding for smokers. This potential anomaly to the nicotine addiction thesis is resolved by the proposition that the reward associated with smoking depends on “high-nicotine boli.” According to the nicotine delivery kinetics hypothesis, smoked nicotine reaches the brain in 5–10 s in high concentrations, which provide reinforcing “hits” of nicotine to the brain. Objectives Because of its essential role in the nicotine addiction thesis, this review set out to examine the current empirical basis of the nicotine delivery kinetics hypothesis. Materials and methods We reviewed studies that bear on two questions: First, does nicotine from cigarettes reach the brain significantly faster than from other nicotine delivery devices? Second, is there a relationship between delivery kinetics and any rewarding effects of nicotine? Results There is little empirical support for the nicotine delivery kinetics hypothesis. Several studies found that arterial nicotine levels associated with smoking are much lower than predicted by the nicotine delivery kinetics thesis and not higher than with other nicotine delivery devices. More importantly, comparisons of nicotine delivery devices with varying speeds of delivery do not suggest any correlation between nicotine delivery profile and subjective reward. Conclusions This review indicates that the wide endorsement of the nicotine delivery kinetics hypothesis is unjustified. Critical research is required to resolve the anomalies within the nicotine addiction theory of smoking.
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Reevaluating the nicotine delivery kinetics hypothesis.
Psychopharmacology, 2007Co-Authors: Reuven Dar, Hanan FrenkAbstract:Rationale The view of smoking as an addiction to nicotine implies that nicotine is an addictive drug and a primary reinforcer. However, nicotine other than in tobacco does not appear to be very rewarding for smokers. This potential anomaly to the nicotine addiction thesis is resolved by the proposition that the reward associated with smoking depends on “high-nicotine boli.” According to the nicotine delivery kinetics hypothesis, smoked nicotine reaches the brain in 5–10 s in high concentrations, which provide reinforcing “hits” of nicotine to the brain.
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Do smokers self-administer pure nicotine? A review of the evidence
Psychopharmacology, 2004Co-Authors: Reuven Dar, Hanan FrenkAbstract:Rationale Nicotine is almost universally believed to be the primary agent motivating tobacco smoking and the main impediment to cessation. A principal argument in support of the presumed reinforcing properties of nicotine is that smokers self-administer pure nicotine. However, the evidence for nicotine self-administration in smokers has not been critically examined. Objectives To review and examine the empirical basis for the assertion that smokers self-administer pure nicotine. Methods We reviewed all the studies we were able to locate that are cited as demonstrating self-administration of nicotine, isolated from tobacco, in normal smokers and non-smokers. These studies investigated self-administration of intravenous nicotine, nicotine gum and nicotine spray. Using the authors’ own criteria, we examined whether these studies in fact demonstrate nicotine-self administration. Results None of the studies we reviewed demonstrated nicotine self-administration in smokers. Both smokers and non-smokers failed to show preference for nicotine over placebo in any of these studies, including in a series of six reports of overnight abstinent smokers having access to nicotine nasal spray, a rapidly absorbed form of nicotine. Conclusions The common statement that smokers self-administer pure nicotine lacks empirical support. Smokers in fact do not administer pure nicotine in any of the forms studied to date, even when abstinent and presumably nicotine-deprived. This conclusion necessitates a critical re-examination of the nicotine addiction thesis.
Maria A. Catania - One of the best experts on this subject based on the ideXlab platform.
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Hypericum perforatum attenuates nicotine withdrawal signs in mice
Psychopharmacology, 2003Co-Authors: Maria A. Catania, Fabio Firenzuoli, Anna Crupi, Carmen Mannucci, Achille P. Caputi, Gioacchino CalapaiAbstract:Rationale Hypericum perforatum is used as a natural antidepressant, and other antidepressants have been marketed to aid in smoking cessation. Objective We investigated the effects of an extract of Hypericum perforatum (Ph-50) on withdrawal signs produced by nicotine abstinence in mice. Methods Nicotine (2 mg/kg, four injections daily) was administered for 14 days to mice. Different doses of Ph-50 (125–500 mg/kg) were administered orally immediately after the last nicotine injection. In another experiment, Ph-50 (500 mg/kg) was orally administered in combination with nicotine, i) starting from day 8 until the end of the nicotine treatment period, or ii) during nicotine treatment and after nicotine withdrawal, or iii) immediately after the last nicotine injection. On withdrawal from nicotine, all animals were evaluated for locomotor activity and abstinence signs. Results The locomotor activity reduction induced by nicotine withdrawal was abolished by Ph-50, which also significantly and dose-dependently reduced the total nicotine abstinence score when injected after nicotine withdrawal. Conclusions These data show that treatment with Hypericum perforatum attenuates nicotine withdrawal signs in mice. Further studies are necessary to test the possibility that it may be used for smoking cessation treatment in humans.
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Hypericum perforatum attenuates nicotine withdrawal signs in mice.
Psychopharmacology, 2003Co-Authors: Maria A. Catania, Fabio Firenzuoli, Anna Crupi, Carmen Mannucci, Achille P. Caputi, Gioacchino CalapaiAbstract:Hypericum perforatum is used as a natural antidepressant, and other antidepressants have been marketed to aid in smoking cessation. We investigated the effects of an extract of Hypericum perforatum (Ph-50) on withdrawal signs produced by nicotine abstinence in mice. Nicotine (2 mg/kg, four injections daily) was administered for 14 days to mice. Different doses of Ph-50 (125–500 mg/kg) were administered orally immediately after the last nicotine injection. In another experiment, Ph-50 (500 mg/kg) was orally administered in combination with nicotine, i) starting from day 8 until the end of the nicotine treatment period, or ii) during nicotine treatment and after nicotine withdrawal, or iii) immediately after the last nicotine injection. On withdrawal from nicotine, all animals were evaluated for locomotor activity and abstinence signs. The locomotor activity reduction induced by nicotine withdrawal was abolished by Ph-50, which also significantly and dose-dependently reduced the total nicotine abstinence score when injected after nicotine withdrawal. These data show that treatment with Hypericum perforatum attenuates nicotine withdrawal signs in mice. Further studies are necessary to test the possibility that it may be used for smoking cessation treatment in humans.
