α‐Amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptor autoradiography in mouse brain after single and repeated withdrawal from diazepam

Allison, Claire; Pratt, Judith A.; Ripley, Tamzin; Stephens, David

doi:10.1111/j.1460-9568.2005.03902.x

Cited by 10 publications

(5 citation statements)

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“…This may be apparent as the increase in hippocampal AMPA binding demonstrated and could result from the removal of GABAergic inhibition following drug withdrawal. This is further supported by recent mouse studies in our laboratories in which there was an increase in AMPA receptor binding in the hippocampus following a single withdrawal from chronic DZP (Allison et al, 2005). These data are also consistent with evidence of increased AMPA binding in the hippocampus 48 h following cessation of 7-day chronic treatment with high doses of flurazepam and increases in hippocampal AMPA receptormediated transmission and withdrawal anxiety 24 h following flurazepam withdrawal (Van Sickle et al, 2004).…”

Section: Hippocampussupporting

confidence: 78%

“…DZP group, a compensatory downregulation of the system may have taken place due to repeated withdrawals, such that [ 3 H]Ro48 8587 binding is now restored to control levels ( Figure 3). Consistent with these results, we have recently reported increases in AMPA receptor binding in these thalamic nuclei in mice experiencing a single withdrawal from chronic DZP (Allison et al, 2005).…”

Section: Thalamussupporting

confidence: 73%

“…DZP increases AMPA receptor binding in mouse hippocampus and amygdala (Allison et al, 2005) consistent with a hypothesis that neuroadaptive changes at the level of the AMPA receptor are involved in the differential effects of these treatment regimes on behavioral measures of withdrawal (Ward and Stephens, 1998;Dunworth and Stephens, 1998;Dunworth et al, 2000). However, neurochemical measures were not directly correlated with behavior in this study and changes in AMPA receptor subunit expression that could affect the functionality of the receptor were not investigated.…”

Section: Introductionmentioning

confidence: 37%

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Differential Effects of Two Chronic Diazepam Treatment Regimes on Withdrawal Anxiety and AMPA Receptor Characteristics

Allison

Pratt

2005

Neuropsychopharmacol

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Withdrawal from chronic benzodiazepines is associated with increased anxiety and seizure susceptibility. Neuroadaptive changes in neural activity occur in limbo-cortical structures although changes at the level of the GABA A receptor do not provide an adequate explanation for these functional changes. We have employed two diazepam treatment regimes known to produce differing effects on withdrawal aversion in the rat and examined whether withdrawal-induced anxiety was accompanied by changes in AMPA receptor characteristics. Rats were given 28 days treatment with diazepam by the intraperitoneal (i.p.) route (5 mg/kg) and the subcutaneous (s.c.) route (15 mg/kg). Withdrawal anxiety in the elevated plus maze was evident in the group withdrawn from chronic s.c. diazepam (relatively more stable plasma levels) but not from the chronic i.p. group (fluctuating daily plasma levels). In the brains of these rats, withdrawal anxiety was accompanied by increased [ 3 H]Ro48 8587 binding in the hippocampus and thalamus, and decreased GluR1 and GluR2 subunit mRNA expression in the amygdala (GluR1 and GluR2) and cortex (GluR1). The pattern of changes was different in the chronic i.p. group where in contrast to the chronic s.c. group, there was reduced [3 H]Ro48 8587 binding in the hippocampus and no alterations in GluR1 and GluR2 subunit expression in the amygdala. While both groups showed reduced GluR1 mRNA subunit expression in the cortex overall, only the agranular insular cortex exhibited marked reductions following chronic i.p. diazepam. Striatal GluR2 mRNA expression was increased in the i.p. group but not the s.c. group. Taken together, these data are consistent with differential neuroadaptive processes in AMPA receptor plasticity being important in withdrawal from chronic benzodiazepines. Moreover, these processes may differ both at a regional and receptor function level according to the behavioral manifestations of withdrawal.

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Section: Hippocampussupporting

confidence: 78%

Section: Thalamussupporting

confidence: 73%

Section: Introductionmentioning

confidence: 37%

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Differential Effects of Two Chronic Diazepam Treatment Regimes on Withdrawal Anxiety and AMPA Receptor Characteristics

Allison

Pratt

2005

Neuropsychopharmacol

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“…Our results differ from other studies that find increases in GluR1 and GluR2B, but no increase in GluR2A mRNA levels in the hippocampus after diazepam treatment [118,119]. Increases in the expression of AMPA receptor subunit mRNAs and AMPA receptor ligand binding have been reported in a number of brain areas after BZ withdrawal [53,289]. We expected that Study 2 would identify increases in GluR1 and GluR2B mRNA, as found in other studies looking at repeated diazepam in mice [118,119].…”

Section: Nmdacontrasting

confidence: 99%

Repeated Zolpidem Treatment Effects on Sedative Tolerance, Withdrawal, mRNA Levels, and Protein Expression

Wright¹

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Zolpidem and benzodiazepines (BZs) potentiate the inhibitory action of gamma-Aminobutyric acid (GABA) by allosterically binding to GABAA receptors (GABAAR). Prolonged use of GABAAR positive allosteric modulators (PAM) can lead to behavioral tolerance, the diminished response to the same drug dose with repeated use, and withdrawal, a group of symptoms that occur due to abrupt end of drug treatment. Zolpidem is a short-acting, non-BZ GABAAR PAM whose potential for tolerance and withdrawal is unclear. Zolpidem demonstrates sedative efficacy similar to BZs and has become a main treatment of insomnia in lieu of BZs. Zolpidem replaced BZs due to lower incidences of tolerance and withdrawal after prolonged treatment and discontinuation. Despite reported lower incidences, some studies find the occurrence of tolerance and withdrawal similar between zolpidem and BZs. Tolerance and withdrawal symptoms are likely caused by drug-induced neuroadaptive changes in central nervous system (CNS) functioning, and these alterations may be similar between zolpidem and BZ. Past rodent research suggests that long term use of zolpidem and BZs may produce alterations in normal inhibitory GABAergic and excitatory glutamatergic functioning in the cortex, hippocampus, amygdala, and PFC and that these alterations may underlie sedative tolerance and withdrawal symptoms. viii TABLE OF CONTENTS CHAPTER 1. INSOMNIA TREATMENT ISSUES.

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“…According to the published data (Dunworth and Stephens 1998 ; Becker et al 1998 ), glutamate neurotransmission is partially responsible for this process. Still, upregulation of transmission mediated via AMPA receptors did not seem to be very important in the enhanced seizure activity after diazepam repeated withdrawal, but intensified AMPA receptor binding in brain areas responsible for emotional responses and seizure activity has been seen in mice subjected to 21-day benzodiazepine treatment alone (Allison et al 2005 ). On the other hand, upregulation of the NMDA receptor seems to play an important role in the hypersusceptibility of the diazepam-withdrawn mice to seizure incidents (Tsuda et al 1998b ).…”

Section: Introductionmentioning

confidence: 99%

NMDA Receptors and NO:cGMP Signaling Pathway Mediate the Diazepam-Induced Sensitization to Withdrawal Signs in Mice

et al. 2017

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The goal of the present study was to examine the effects of N-methyl—aspartate (NMDA) receptor antagonists—memantine and ketamine and the drugs modifying the NO:cGMP pathway—NG-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), the endogenous precursor of NO-L-arginine, and the guanylyl cyclase inhibitor—methylene blue (MB) on the development of sensitization to withdrawal signs precipitated after chronic, interrupted treatment with diazepam, a benzodiazepine receptor agonist, in mice. To develop the sensitization, the mice were divided into groups: continuously and sporadically (with two diazepam-free periods) treated with diazepam (15 mg/kg, sc). To precipitate the withdrawal syndrome (clonic and tonic seizures, and death), pentylenetetrazole (55 mg/kg, sc) with the benzodiazepine receptor antagonist, flumazenil (5.0 mg/kg, ip), were administered after the last injection of diazepam or saline. Memantine (2.5, 5.0 mg/kg), and ketamine (2.5, 5.0 mg/kg), L-NAME (100, 200 mg/kg) and 7-NI (20 and 40 mg/kg), L-arginine (250, 500 mg/kg) and MB (5 and 10 mg/kg) were administered ip in sporadically diazepam-treated mice during the diazepam-free periods. Our results indicated that both NMDA receptor antagonists and drugs that inhibit the NO:cGMP pathway, except L-arginine (the endogenous donor of NO), attenuated the diazepam-induced sensitization to withdrawal signs in mice. Thus, NMDA receptors and the NO:cGMP pathway are involved in the mechanisms of sensitization to benzodiazepine withdrawal.

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α‐Amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptor autoradiography in mouse brain after single and repeated withdrawal from diazepam

Cited by 10 publications

References 58 publications

Differential Effects of Two Chronic Diazepam Treatment Regimes on Withdrawal Anxiety and AMPA Receptor Characteristics

Differential Effects of Two Chronic Diazepam Treatment Regimes on Withdrawal Anxiety and AMPA Receptor Characteristics

Repeated Zolpidem Treatment Effects on Sedative Tolerance, Withdrawal, mRNA Levels, and Protein Expression

NMDA Receptors and NO:cGMP Signaling Pathway Mediate the Diazepam-Induced Sensitization to Withdrawal Signs in Mice

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