Abstract:
RATIONALE:Chronic administration of nicotine in rats results in upregulation of neuronal nicotinic receptors. Upregulation has been proposed to reflect receptor desensitization, which may underlie functional tolerance to nicotine's effects. However, evidence indicates that tolerance and upregulation do not always parallel each other, suggesting that either upregulation does not always reflect desensitization, or mechanisms other than receptor desensitization account for tolerance to nicotine. OBJECTIVES:The present studies examined tolerance to nicotine-induced antinociception and changes in receptor binding after two regimens of intermittent nicotine injections in rats. The role of receptor activation in upregulation and tolerance was also examined by co-administering nicotine with the non-competitive antagonist, mecamylamine. METHODS:Sprague-Dawley rats were administered a short (once-daily, s.c. for 6 days (0.35 mg/kg)) or long (twice-daily for 11 days (0.66 mg/kg)) series of injections and tolerance to nicotine-induced antinociception and [3H]epibatidine binding in whole brain were measured. RESULTS:The short series of injections resulted in tolerance to nicotine-induced antinociception, but failed to increase [3H]epibatidine binding. In contrast, the long series of injections resulted in both tolerance and increased receptor binding. Once-daily pairings of mecamylamine (1 mg/kg, s.c.) with nicotine (0.35 mg/kg) for 6 days blocked the development of tolerance, indicating receptor activation is necessary for tolerance to occur. Pairing mecamylamine with nicotine (0.66 mg/kg) twice daily for 11 days blocked tolerance but produced a greater increase in [3H]epibatidine binding than nicotine alone. CONCLUSIONS:A dissociation of tolerance from receptor upregulation was observed in the present study. The finding that receptor activation may be necessary for tolerance but not upregulation is discussed within the context of possible mechanisms controlling tolerance to nicotine.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
McCallum SE,Caggiula AR,Booth S,Breese CR,Lee MJ,Donny EC,Leonard S,Sved AFdoi
10.1007/s002130000401subject
Has Abstractpub_date
2000-05-01 00:00:00pages
1-8issue
1eissn
0033-3158issn
1432-2072journal_volume
150pub_type
杂志文章abstract::In an attempt to define the nature of the involvement of delta 9-tetrahydrocannabinol (THC) with central cholinergic neurotransmission, the effects of THC on direct cholinergic stimulation of the rat brain were investigated. THC, in doses of 3 mg/kg and 6 mg/kg, administered intraperitoneally (i.p.), potentiated the e...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00426661
更新日期:1979-02-28 00:00:00
abstract::Medial thalamic (MT), and hippocampal (HPC) EEG, and single unit activity, and frontal cortical (CTX) EEG were recorded following IV infusions of 0.625 mg morphine/kg in drug-naive, and following 0.0125 mg naloxone/kg in morphine-dependent paralyzed rats. Particular effort was made to assess the latency of the respons...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00433246
更新日期:1980-01-01 00:00:00
abstract::Triadimefon is a triazole fungicide that produces hyperactivity in both mice and rats similar to that seen following administration of compounds with catecholaminergic activity (e.g., d-amphetamine). To determine whether the triadimefon-induced hyperactivity is due to an action on CNS catecholaminergic systems, we eva...
journal_title:Psychopharmacology
pub_type: 杂志文章
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journal_title:Psychopharmacology
pub_type: 杂志文章
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更新日期:1992-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
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更新日期:1986-01-01 00:00:00
abstract:RATIONALE:The rapid membrane actions of neuroactive steroids, particularly via an enhancement of γ-aminobutyric acidA receptors (GABAARs), participate in the regulation of central nervous system excitability. Prior evidence suggests an inverse relationship between endogenous GABAergic neuroactive steroid levels and beh...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-014-3618-y
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abstract:RATIONALE:Reductions in cue-induced craving and subjective response to drugs of abuse are commonly used as initial outcome measures when testing novel medications for the treatment of addiction. Yet neither the relationship between these two measures at the individual level nor the moderating effects of pharmacotherapi...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-017-4607-8
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427569
更新日期:1983-01-01 00:00:00
abstract::Because of the increasing demand for refined techniques to record drug-induced motoric changes, we designed and evaluated a computer monitoring system with continuous measurement of different parameters of rat motor activity. This system is particularly useful for chronic drug studies because it can characterize patte...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00432113
更新日期:1983-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
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journal_title:Psychopharmacology
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更新日期:2005-11-01 00:00:00
abstract:RATIONALE:Approximately 20 million adults in the USA have an alcohol use disorder (AUD). There are clinical and preclinical data suggesting that psychedelics may have benefits for AUD. OBJECTIVE:To investigate the effects of the synthetic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) on the behavioral effects of e...
journal_title:Psychopharmacology
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abstract::The effects of single and long-term haloperidol administration on rat open field behavior was studied. Withdrawal from long-term haloperidol treatment induced a significant increase in all parameters of activity recorded, except rearing. There was a direct relationship between the impairment of motor function induced ...
journal_title:Psychopharmacology
pub_type: 杂志文章
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更新日期:1981-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:1987-01-01 00:00:00
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更新日期:2012-05-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245288
更新日期:1992-01-01 00:00:00
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更新日期:2008-12-01 00:00:00
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更新日期:2012-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2016-10-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
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更新日期:1981-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
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更新日期:1978-04-14 00:00:00
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更新日期:1987-01-01 00:00:00
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更新日期:1982-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章,已发布勘误
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更新日期:2018-09-01 00:00:00
abstract:RATIONALE:Nicotine replacement is commonly used to treat tobacco use in heavy-drinking smokers. However, few studies have examined the effect of nicotine replacement on subjective and physiological responses to alcohol and alcohol drinking behavior. OBJECTIVE:The primary aim of this within-subject, double-blind study ...
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pub_type: 临床试验,杂志文章
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更新日期:2008-02-01 00:00:00
abstract:RATIONALE:Only a small percentage of individuals seeking treatment for their marijuana use achieves sustained abstinence, suggesting more treatment options are needed. OBJECTIVES:We investigated the effects of baclofen (study 1) and mirtazapine (study 2) in a human laboratory model of marijuana intoxication, withdrawa...
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更新日期:2010-08-01 00:00:00