Cholinergic mechanisms in physical dependence on barbiturates, ethanol and benzodiazepines

Nordberg, Agneta; Wahlström, Göran

doi:10.1007/bf01244733

Cited by 34 publications

(13 citation statements)

References 90 publications

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“…The primary components involve a decrease in sensitivity in the target tissue when this tissue is influenced by an active concentration of the drug (tolerance at the receptor site). However, the decreased function can also partly be compensated by increased activity in other brain systems as illustrated by the activity in the muscarinic component of the cholinergic system after long‐term exposure to barbiturate, ethanol and benzodiazepines (Nordberg and Wahlstrom, 1992). A related compensatory brain mechanism is the learned behavioural or conditioned tolerance.…”

Section: Definitions Of Tolerancementioning

confidence: 99%

“…The development of ethanol tolerance and dependence is associated with alterations in many receptor systems (Nordberg and Wahlstrom, 1992; Hoffman et al ., 2000; Chastain, 2006). The properties of the GABA‐A receptors are influenced, as well as alterations have been recorded in the expression of distinct GABA‐A receptor subunit mRNA and peptides in various brain regions.…”

Section: Tolerance To Substances Active At Gabaergic Systemmentioning

confidence: 99%

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Tolerance to allopregnanolone with focus on the GABA‐A receptor

Türkmen

Bäckström

Wahlström

et al. 2010

British J Pharmacology

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Many studies have suggested a relationship between stress, sex steroids, and negative mental and mood changes in humans. The progesterone metabolite allopregnanolone is a potent endogenous ligand of the g-amino butyric acid -A (GABA-A) receptor, and the most discussed neuroactive steroid. Variations in the levels of neuroactive steroids that influence the activity of the GABA-A receptor cause a vulnerability to mental and emotional pathology. There are physiological conditions in which allopregnanolone production increases acutely (e.g. stress) or chronically (e.g. menstrual cycle, pregnancy), thus exposing the GABA-A receptor to high and continuous allopregnanolone concentrations. In such conditions, tolerance to allopregnanolone may develop. We have shown that both acute and chronic tolerances can develop to the effects of allopregnanolone. Following the development of acute allopregnanolone tolerance, there is a decrease in the abundance of the GABA-A receptor a4 subunit and the expression of the a4 subunit mRNA in the ventral-posteriomedial nucleus of the thalamus. Little is known about the mechanism behind allopregnanolone tolerance and its effects on assembly of the GABA-A receptor composition. The exact mechanism of the allopregnanolone tolerance phenomena remains unclear. The purpose of this review is to summarize certain aspects of current knowledge concerning allopregnanolone tolerance and changes in the GABA-A receptors. AbbreviationsCNS, central nervous system; EEG, electroencephalography; GABA-A, g-amino butyric acid -A; HRT, hormone replacement therapy; NMDA, N-methyl-D-aspartic acid; PMDD, premenstrual dysphoric disorder; PMS, premenstrual syndrome; SS, burst suppression of 1 s or more in the EEG (silent second); THDOC, tetrahydro-deoxycorticosterone; VPM, ventral-posteriomedial nucleus IntroductionThe development of tolerance to foreign compounds with effects in the central nervous system (CNS) is a common phenomenon. Whether tolerance can occur with endogenous substances and in specific disorders is less well known. The purpose of this review is to examine the possibility that chronic production of steroids active on the g-amino butyric acid -A (GABA-A) receptor may induce tolerance under certain conditions. In particular, inhibitory compounds working on the GABA-A receptor are known to induce tolerance. Well-known examples are benzodiazepines, barbiturates and alcohol, all of which enhance the inhibitory effect of GABA on the chloride ion flux through the GABA-A receptor (Allan et al., 1992;Pesold et al., 1997;Wallace et al., 2007). Endogenous GABA-A receptor agonists exist in the 3a-hydroxy metabolites of progesterone, testosterone and deoxycorticosterone, known as allopregnanolone, pregnanolone, androstanediol and tetrahydrodeoxycorticosterone (THDOC). These compounds are steroids and act as agonists at the GABA-A receptor, and hence are known as GABA steroids (Mellon and Griffin, 2002;Backstrom et al., 2003). The first evidence for the development of tolerance to chronic pregnanolone exposur...

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Section: Definitions Of Tolerancementioning

confidence: 99%

Section: Tolerance To Substances Active At Gabaergic Systemmentioning

confidence: 99%

Tolerance to allopregnanolone with focus on the GABA‐A receptor

Türkmen

Bäckström

Wahlström

et al. 2010

British J Pharmacology

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“…Here, we will focus on heroin, phenobarbital and chlorpyrifos. These substances obviously differ in their chemical class and basic mechanisms of action, but all three nevertheless converge on the development of hippocampal cholinergic innervation [32,33,55,57]. We previously established that prenatal treatment of HS/Ibg heterogeneous stock mice [28] with these teratogens evoked persistent presynaptic hyperactivity, evidenced by increases in the concentration of choline transporter sites [44,56] and by a tonic increase in ACh release [1].…”

Section: Complementary Neurobehavioral Teratogenicity Modelsmentioning

confidence: 99%

A mechanism-based complementary screening approach for the amelioration and reversal of neurobehavioral teratogenicity

Yanai

Brick-Turin

Dotan

et al. 2010

Neurotoxicology and Teratology

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The identification of mechanisms and outcomes for neurobehavioral teratogenesis is critical to our ability to develop therapies to ameliorate or reverse the deleterious effects of exposure to developmental neurotoxicants. We established mechanistically-based complementary models for the study of cholinergic systems in the mouse and the chick, using both environmental neurotoxicants (chlorpyrifos, perfluoroalkyls) and drugs of abuse (heroin, nicotine, PCP). Behavioral evaluations were made using the Morris maze in the mouse, evaluating visuospatial memory related to hippocampal cholinergic systems, and imprinting in the chick, examining behavior dependent on cholinergic innervation of the IMHV. In both models we demonstrated the dependence of neurobehavioral deficits on impairment of cholinergic receptor-induced expression, and translocation of specific PKC isoforms. Understanding this mechanism, we were able to reverse both the synaptic and behavioral deficits with administration of neural progenitors. We discuss the prospects for clinical application of neural progenitor therapy, emphasizing protocols for reducing or eliminating immunologic rejection, as well as minimizing invasiveness of procedures through development of intravenous administration protocols. KeywordsChick; Induction of endogenous cells; Mouse; Neural progenitor transplantation; Neurobehavioral teratogenicity Complementary neurobehavioral teratogenicity modelsAn inherent methodological obstacle in studies of the mechanisms of neurobehavioral teratogenicity is the problem of specificity; most neuroteratogens affect multiple regions and processes, resulting in plethora of behavioral defects. It is thus critical to develop exposure models that produce functional (behavioral) deficits linked to specific neurotransmitter and synaptic mechanisms. Accordingly, the principal approach taken in our studies has been to

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“…Nicotine is a major component in tobacco and plays a principal role on psychological and neurological changes induced by smoking. Activation of nicotinic acetylcholine (nACh) receptors in brain releases various types of neurotransmitters (such as dopamine, serotonin, acetylcholine, and norepinephrine), which in turn exert neuropsychological effects (alertness, decreased anxiety, and increased efficacy of learning memory and working) 7. Repeated administration of nicotine induces dependence, and its cessation produces anxiety, depression, sleep disturbance, increased tension, and increased appetite, which are taken as indications of withdrawal syndrome.…”

Section: Dbi and Drug Dependencementioning

confidence: 99%

Pharmacological Basis for Management of Drug Dependence

Katsura

Ohkuma

2004

Annals of the New York Academy of Sciences

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Neurochemical mechanisms underlying development of drug dependence and withdrawal syndrome remain unclear. Several clinical features of withdrawal syndrome, such as anxiety, are considered to be common among patients with drug dependence induced by different drugs of abuse. In the present study, we investigated whether diazepam-binding inhibitor (DBI), an endogenous anxiogenic neuropeptide, participates in the anxiety associated with drug dependence and its withdrawal symptoms. When we examined brain from mice dependent on alcohol, nicotine, and morphine, we observed that the levels of DBI protein and its mRNA significantly increased. Abrupt cessation of these drugs facilitated further increases in DBI expression. In the cases of nicotine- and morphine-dependent mice, concomitant administration of specific antagonists for nicotinic acetylcholine and m-opioid receptors, respectively, abolished the increased expression. Similar patterns of DBI expression were observed in the neurons after sustained exposure to these drugs and its removal from culture medium. Sustained exposure of the neurons to abused drugs significantly increased the KCl (30 mM)-induced 45Ca2+ influx and enhanced expression of alpha1 subunits for L-type high voltage-gated Ca2+ channels (HVCCs). In addition, the increase in DBI expression was completely blocked by L-type HVCC inhibitors. Therefore, these alterations in DBI expression, mediated via increased influx of Ca2+ through upregulated L-type HVCCs, are closely related to drug dependence and/or its withdrawal syndrome and are considered to be part of a common biochemical process in drug dependence induced by different drugs of abuse.

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Cholinergic mechanisms in physical dependence on barbiturates, ethanol and benzodiazepines

Cited by 34 publications

References 90 publications

Tolerance to allopregnanolone with focus on the GABA‐A receptor

Tolerance to allopregnanolone with focus on the GABA‐A receptor

A mechanism-based complementary screening approach for the amelioration and reversal of neurobehavioral teratogenicity

Pharmacological Basis for Management of Drug Dependence

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