A lack of tolerance to the anxiolytic effects of diazepam on the plus-maze: comparison of male and female rats

Stock, Howard S.; Foradori, Chad D.; Ford, Kris; Wilson, Marlene A.

doi:10.1007/s002130050004

Cited by 37 publications

(19 citation statements)

References 51 publications

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“…In rats receiving the control virus (DSGZ), diazepam administration did not significantly alter anxiety measures in the elevated plus maze (percent time spent in open arms, Figure 2; F(1,40) = 0.3, p=0.6 for diazepam effect), however, diazepam increased locomotor activity (number of closed arm entries, Figure 3), (F(1,40) =6.9, p<0.02). These results are similar to those reported earlier (Stock et al 2000;Kang et al 2000;Wilson et al 2004), in that these doses of diazepam produce marginal anxiolytic effects in male rats, with or without a lacZ (control) virus injection, under these test conditions. Naltrindole administration did not affect anxiety (F(1,40) = 0.3), or activity (F(1,40) = 0.01) measures in vehicle or diazepam-treated control (DSGZ) rats (p > 0.05).…”

Section: Experiments 1: Effect Of a Delta Opioid Antagonist On Enkephasupporting

confidence: 91%

The role of delta opioid receptors in the anxiolytic actions of benzodiazepines

Primeaux

Wilson

McDonald

et al. 2006

Pharmacology Biochemistry and Behavior

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The anxiolytic effects of benzodiazepines appear to involve opioid processes in the amygdala. In previous experiments, overexpression of enkephalin in the amygdala enhanced the anxiolytic actions of the benzodiazepine agonist diazepam in the elevated plus maze. The effects of systemically administered diazepam are also blocked by injections of naltrexone into the central nucleus of the amygdala. The current studies investigated the role of delta opioid receptors in the anxiety-related effects of diazepam. Three days following bilateral stereotaxic injections of viral vectors containing cDNA encoding proenkephalin or β-galactosidase (control vector), the delta opioid receptor antagonist naltrindole (10 mg/kg, s.c.) attenuated the enhanced anxiolytic effects of 1-2 mg/kg diazepam in rats overexpressing preproenkephalin in the amygdala. Despite this effect, naltrindole failed to attenuate the anxiolytic action of higher diazepam doses (3 mg/kg) in animals with normal amygdalar enkephalin expression. Similarly, the mu opioid receptor antagonist, β-funaltrexamine (20mg/kg, sc), had no effect on the anxiolytic effect of diazepam alone. These data support a role for delta opioid receptors in the opioid-enhanced anxiolytic effects of diazepam.

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Section: Experiments 1: Effect Of a Delta Opioid Antagonist On Enkephasupporting

confidence: 91%

The role of delta opioid receptors in the anxiolytic actions of benzodiazepines

Primeaux

Wilson

McDonald

et al. 2006

Pharmacology Biochemistry and Behavior

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“…Drugs that increase the open arms exploration are considered anxiolytics and the reverse holds true for anxiogenic compounds (Handley and McBlane, 1993). In this study, diazepam was used as a positive control and, as expected, it increased the activity in the open arms of the elevated plus-maze apparatus, confirming its anxiolytic actions (Stock et al, 2000). Many benzodiazepines, and related compounds that bind to receptors in the central nervous system, have been already identified in certain plant extracts Medina and Marder, 1996;Viola et al, 1994Viola et al, , 1995.…”

Section: Discussionmentioning

confidence: 53%

The anxiolytic-like effects of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) in mice

Hellión-Ibarrola

Ibarrola

Montalbetti

et al. 2006

Journal of Ethnopharmacology

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“…Our pharmacological findings are supported by the Western blot data demonstrating almost undetectable levels of α4 expression in the CA1 hippocampus of diestrous female rats. Gender differences in both subunit composition and GABA pharmacology have been widely reported Stock et al, 2000;Yee et al, 2004), so this pharmacological difference is not surprising.…”

Section: Discussionmentioning

confidence: 96%

Short-term steroid treatment increases δ GABAA receptor subunit expression in rat CA1 hippocampus: Pharmacological and behavioral effects

et al. 2005

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In this study, 48 h administration of 3α-OH-5β-pregnan-20-one (3α,5β-THP) or 17β-estradiol (E 2 )+progesterone (P) to female rats increased expression of the δ subunit of the GABA A receptor (GABAR) in CA1 hippocampus. Coexpression of α4 and δ subunits was suggested by an increased response of isolated pyramidal cells to the GABA agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), following 48 h steroid treatment, and nearly complete blockade by 300 μM lanthanum (La 3+ ). Because α4βδ GABAR are extrasynaptic, we also recorded pharmacologically isolated GABAergic holding current from CA1 hippocampal pyramidal cells in the slice. The La 3+ -sensitive THIP current, representative of current gated by α4βδ GABAR, was measurable only following 48 h steroid treatment. In contrast, the bicucullinesensitive current was not altered by steroid treatment, assessed with or without 200 nM gabazine to block synaptic current. However, 48 h steroid treatment resulted in a tonic current insensitive to the benzodiazepine agonists lorazepam (10 μM) and zolpidem (100 nM). These results suggest that 48 h steroid treatment increases expression of α4βδ GABAR which replace the ambient receptor population. Increased anxiolytic effects of THIP were also observed following 48 h steroid treatment. The findings from the present study may be relevant for alterations in mood and benzodiazepine sensitivity reported across the menstrual cycle.

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A lack of tolerance to the anxiolytic effects of diazepam on the plus-maze: comparison of male and female rats

Cited by 37 publications

References 51 publications

The role of delta opioid receptors in the anxiolytic actions of benzodiazepines

The role of delta opioid receptors in the anxiolytic actions of benzodiazepines

The anxiolytic-like effects of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) in mice

Short-term steroid treatment increases δ GABAA receptor subunit expression in rat CA1 hippocampus: Pharmacological and behavioral effects

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