Neuropharmacology of Sedatives and Anxiolytics

Schallek, William; Schlosser, Walter

doi:10.1159/000401211

Cited by 11 publications

(6 citation statements)

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“…4a) appeared to be similar to the defensive response recognized in an animal model of panic anxiety [33]. Generally, anxiety is induced by hyperexcitability in the amygdalar and hippocampal neural circuits under certain circumstances, and benzodiazepines act as anxiolytic agents by enhancing presynaptic inhibition mediated by c-aminobutylic acid (GABA) in neural circuits especially in the medial nucleus of the amygdala [34]. It is interesting to speculate that the decrease in the immobility time in the tail suspension test (Fig.…”

Section: Discussionsupporting

confidence: 55%

Withdrawal from Fixed-Dose Injection of Methamphetamine Decreases Cerebral Levels of 3-Methoxy-4-hydroxyphenylglycol and Induces the Expression of Anxiety-Related Behavior in Mice

Kitanaka

Tatsuta

et al. 2010

Neurochem Res

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A variety of drug treatment regimens have been proposed to model the dysphoric state observed during methamphetamine (METH) withdrawal in rats, but little has been established in experiments using mice. In male ICR mice, a fixed-dose injection regimen of METH (1.0 or 2.5 mg/kg, i.p., twice daily for 10 consecutive days) induced a significant decrease in the time spent in open arms in an elevated plus maze after 5 days of drug abstinence. Under an escalating-dose injection regimen (0.2-2.0 mg/kg, i.p., 3 times daily for 4 days, total: 15 mg/kg/animal) or continuous subcutaneous administration with osmotic mini-pumps (15 or 76 mg/kg of METH for 2 weeks), no significant behavioral change was observed after 5 days of drug abstinence, compared with control animals. Reduced gains in body weight were observed during repeated treatment with METH in the fixed-dose injection and mini-pump treatment regimens, but not the escalating-dose injection regimen. HPLC analysis revealed significant decreases in the level of cerebral 3-methoxy-4-hydroxyphenylglycol, a norepinephrine metabolite, and norepinephrine turnover, which may be attributed to the expression of anxiety-related behavior in the elevated plus maze. These observations suggest that the mice treated with a fixed-dose of METH may model the anxiety-related behavior observed in the dysphoric state induced by METH withdrawal in humans.

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Section: Discussionsupporting

confidence: 55%

Withdrawal from Fixed-Dose Injection of Methamphetamine Decreases Cerebral Levels of 3-Methoxy-4-hydroxyphenylglycol and Induces the Expression of Anxiety-Related Behavior in Mice

Kitanaka

Tatsuta

et al. 2010

Neurochem Res

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“…Therefore, the similarities in the sleep alterations induced by progesterone and allopregnanolone may also be due to the prominent agonistic modulatory interaction of the latter with GABA A receptors. In keeping with this activity, their sleep profile is very reminiscent of that evoked by other agonistic modulators of GABA A receptors, such as barbiturates, benzodiazepines, zopiclone and zolpidem (Oswald et al 1963;Gottesmann 1964;Baekland 1967;Gaillard et al 1973;Schallek and Schlosser 1979;Borbély et al 1985;Dijk et al 1989;Mendelson and Martin 1990;Trachsel et al 1990;Brunner et al 1991;Gandolfo et al 1994;Lancel et al 1996a). These observations strongly suggest that progesterone affects sleep indirectly, via an allosteric agonistic modulatory action of its metabolite allopregnanolone on GABA A receptor functioning.…”

Section: Progesteronementioning

confidence: 92%

“…However, GABAergic processes are established to play a key role in the generation of spindles: spindle oscillations are triggered in the GABAergic reticular thalamic nucleus (reviewed in Steriade et al 1993). Agonistic modulators of GABA A receptors consistently facilitate the occurrence of sleep spindles (Schallek and Schlosser 1979;Borbély et al 1985;Dijk et al 1989;Trachsel et al 1990;Brunner et al 1991;Nuñez et al 1992;Lancel et al 1996aLancel et al , 1997b. Moreover, in vitro experiments showed that spindle frequencies are abolished by the GABA A receptor antagonist bicuculline (von Krosigk et al 1993), while flumazenil has been found to antagonize benzodiazepine-induced spindling in vivo (Gaillard and Blois 1989).…”

Section: Picrotoxin and Progesteronementioning

confidence: 99%

“…Drugs of both classes are able to shorten non-REMS latency, to promote non-REMS or its substate pre-REMS and to decrease REMS (Oswald et al 1963;Gottesmann 1964;Baekland 1967;Gaillard et al 1973;Borbély et al 1985;Mendelson and Martin 1990;Gandolfo et al 1994;Lancel et al 1996a). While barbiturates are established to augment spindling within non-REMS (reviewed in Schallek and Schlosser 1979), benzodiazepines consistently decrease slow EEG components and enhance EEG activity in the frequency range of sleep spindles in humans (Borbély et al 1985;Dijk et al 1989;Trachsel et al 1990) and also in the higher frequency bands in rats (Lancel et al 1996a(Lancel et al , 1997a.…”

Section: Introductionmentioning

confidence: 99%

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The GABA A receptor antagonist picrotoxin attenuates most sleep changes induced by progesterone

et al. 1999

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Progesterone has been shown to exert benzodiazepine-like effects on sleep, which suggests that they are mediated by an agonistic modulation of GABA(A) receptor functioning. To assess the involvement of GABA(A) receptors, we investigated the sleep responses to one dose of the GABA(A) antagonist picrotoxin (1.5 mg/kg) and progesterone (90 mg/kg), administered IP to eight rats alone and in combination, during the first 4 post-injection hours. Compared with vehicle, picrotoxin significantly delayed the latency to non-rapid eye movement sleep (non-REMS) and thereby decreased all sleep states, but barely affected the EEG activity within non-REMS. Progesterone significantly shortened non-REMS latency, increased pre-REMS, depressed low-frequency EEG activity (< or = 8 Hz) and augmented EEG activity in the higher frequencies within non-REMS. Except for the changes in high-frequency EEG activity, picrotoxin attenuated all effects of progesterone. These findings support the notion that GABA(A) receptors play an important role in the sleep effects of progesterone.

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“…Intensive stress attenuates inhibitory GABAergic control in the BLA (Braga et al, 2002;Rodriguez Manzanares et al, 2005), which appears to be responsible for behavioral impairments resulting from stress (Minor and Hunter, 2002). In addition, many drugs for mood and anxiety disorders achieve their therapeutic effects at least partially by modifying the GABAergic system in the amygdala (Millan, 2003;Schallek and Schlosser, 1979). Hence, stress-induced alteration of GABAergic transmission in the amygdala may be an important pathophysiological mechanism underlying anxiety and stress disorders, such as posttraumatic stress disorder (PTSD) and depressive illnesses.…”

Section: Introductionmentioning

confidence: 99%

Stress Impairs 5-HT2A Receptor-Mediated Serotonergic Facilitation of GABA Release in Juvenile Rat Basolateral Amygdala

Jiang

Xing

Yang

et al. 2008

Neuropsychopharmacol

130

123

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The occurrence of stress and anxiety disorders has been closely associated with alterations of the amygdala GABAergic system. In these disorders, dysregulation of the serotonergic system, a very important modulator of the amygdala GABAergic system, is also well recognized. The present study, utilizing a learned helplessness stress rat model, was designed to determine whether stress is capable of altering serotonergic modulation of the amygdala GABAergic system. In control rats, administration of 5-HT or a-methyl-5-HT, a 5-HT 2 receptor agonist, to basolateral amygdala (BLA) slices dramatically enhanced frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). This effect was blocked by selective 5-HT 2A receptor antagonists while a selective 5-HT 2B receptor agonist and a selective 5-HT 2C receptor agonist were without effect on sIPSCs. Double immunofluorescence labeling demonstrated that the 5-HT 2A receptor is primarily localized to parvalbumin-containing BLA interneurons. Thus, serotonin primarily acts via 5-HT 2A receptors to facilitate BLA GABAergic inhibition. In stressed rats, the 5-HT 2A receptor-mediated facilitative actions were severely impaired. Quantitative RT-PCR and western blot analysis showed that the impairment of 5-HT 2A receptor signaling primarily resulted from receptor downregulation. The stress-induced effect appeared to be specific to 5-HT 2A receptors because stress had no significant impact on other serotonin receptors, as well as histamine H 3 receptor and a 2 adrenoceptor signaling in the BLA. This severe impairment of 5-HT 2A receptor-mediated facilitation of BLA GABAergic inhibition might result in an amygdala circuitry with hyperexcitability, and a lower threshold of activation, and thus be an important mechanism underlying the emergence of stress-associated psychiatric symptoms.

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Neuropharmacology of Sedatives and Anxiolytics

Cited by 11 publications

References 0 publications

Withdrawal from Fixed-Dose Injection of Methamphetamine Decreases Cerebral Levels of 3-Methoxy-4-hydroxyphenylglycol and Induces the Expression of Anxiety-Related Behavior in Mice

Withdrawal from Fixed-Dose Injection of Methamphetamine Decreases Cerebral Levels of 3-Methoxy-4-hydroxyphenylglycol and Induces the Expression of Anxiety-Related Behavior in Mice

The GABA A receptor antagonist picrotoxin attenuates most sleep changes induced by progesterone

Stress Impairs 5-HT2A Receptor-Mediated Serotonergic Facilitation of GABA Release in Juvenile Rat Basolateral Amygdala

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