Flumazenil but not nitrendipine reverses the increased anxiety during ethanol withdrawal in the rat

File, Sandra E.; Baldwin, Helen A.; Hitchcott, Paul Kenneth

doi:10.1007/bf00444702

Cited by 110 publications

(89 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chronic ethanol exposure has been associated with emotional hyperactivity in rodents and humans (Cooper et al, 1979;Glue and Nutt, 1990). Stress-like effects produced by withdrawal from chronic ethanol have been previously studied in rats using the social interaction test (File et al, 1989) and the elevated plus-maze (Baldwin et al, 1991). In these experiments, significant withdrawal signs are observed approximately 8-10 hr after ethanol withdrawal.…”

Section: Discussionmentioning

confidence: 99%

Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis

et al. 1995

View full text Add to dashboard Cite

Previous research has suggested a role for corticotropin-releasing factor (CRF) in the anxiogenic effects of stressful stimuli and ethanol withdrawal. This hypothesis was explored in a series of experiments using intracranial microdialysis to monitor CRF-like immunoreactivity (CRF-IR) in the extracellular compartment of the rat amygdala. The synaptic origin of CRF-IR release in the amygdala was determined in vitro by assessing the Ca2+ dependency of 4-aminopyridine stimulated CRF-IR release from tissue preparations of rat amygdala. In vivo experiments were performed in awake rats after the placement of microdialysis probes in the amygdala. In the first experiment, transient restraint stress (20 min) produced an increase of CRF-IR release (basal levels, 1.19 +/- 0.15 fmol/50 microliters; stress levels, 4.54 +/- 1.33 fmol/50 microliters; p < 0.05) that returned to basal values within 1 hr. When 4-aminopyridine (5 mM) was added to the perfusion medium, it consistently increased CRF-IR release (4.83 +/- 0.92 fmol/50 microliters, p < 0.05). In the second experiment, CRF-IR release was measured during ethanol withdrawal in rats previously maintained for 2–3 weeks on a liquid diet containing ethanol (8.5%). Basal CRF-IR levels were 2.10 +/- 0.43 fmol/50 microliters in ethanol exposed rats and 1.30 +/- 0.19 fmol/50 microliters in control rats. During withdrawal, a progressive increase of CRF-IR levels over time was observed, reaching peak values at 10–12 hr after the onset of withdrawal (10.65 +/- 0.49 fmol/50 microliters vs 1.15 +/- 0.30 fmol/50 microliters of control rats, p < 0.01).

show abstract

Section: Discussionmentioning

confidence: 99%

Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis

et al. 1995

View full text Add to dashboard Cite

show abstract

“…This test involves placing a pair of animals in an arena and measuring the amount of time engaged in such behaviors as grooming, sniffing, crawling over or under, and boxing; locomotor activity is simultaneously recorded and provides a measure that is independent of social interaction (File, 1980). Social interaction has been repeatedly validated as an index of anxiety-related behavior because it is decreased following anxiety-provoking stimuli, such as bright lights or exposure to cat odor (File, 1980;File and Hyde, 1978), after administration of anxiogenic drugs (e.g., Battacharya et al, 1997;File and Lister, 1984;Guy and Gardner, 1985;Sams-Dodd, 1995) or following withdrawal from drugs of abuse, including ethanol (Andrews et al, 1997;File et al, 1989;Irvine et al, 2001;Kampov-Polevoy et al, 2000;Overstreet et al, 2002). Conversely, social interaction can be increased by prior exposure to the test arena (File, 1980;File and Hyde, 1978) or the administration of anxiolytic drugs at doses that have little effect on locomotor activity (Barnes et al, 1990;File, 1980;Lightowler et al, 1994).…”

Section: Social Interaction Testmentioning

confidence: 99%

Modulation of multiple ethanol withdrawal-induced anxiety-like behavior by CRF and CRF1 receptors

Overstreet

Knapp

Breese

2004

Pharmacology Biochemistry and Behavior

154

153

View full text Add to dashboard Cite

Previous work demonstrated that rats subjected to multiple withdrawals from chronic ethanol exhibit a sensitization of anxiety-like behavior compared to animals withdrawn from treatment with an equal but continuous amount of ethanol. This study sought to examine whether corticotropin-releasing factor (CRF) could modulate this ethanol-withdrawal-induced anxiety-like behavior. Initially, rats were administered with CRF (1 μg) or vehicle intraventricularly on two occasions 5 days apart while on control diet (CD) followed by exposure to 7% ethanol diet (ED) for 5 days, with social interaction assessed 5 h into withdrawal. Social interaction was significantly reduced in the CRF-treated animals compared to vehicle-treated rats and vehicle-and CRF-treated rats maintained on CD, indicative that CRF given before ethanol exposure was capable of inducing an adaptive change that sensitized withdrawal-induced anxiety-like behavior. Next, the CRF 1 receptor antagonist CRA1000 (3 mg/kg, systemically), the CRF 2 receptor antagonist antisauvagine-30 (20 μg intraventricularly), or vehicle was injected 4 h after the ethanol was removed following the first and second cycles of chronic ethanol exposure and the effect on the multiple-withdrawal-induced anxiety-like behavior determined after the third withdrawal cycle. The CRF 1 receptor antagonist blocked the reduced social interaction behavior, whereas the CRF 2 receptor antagonist was without effect. Similar pretreatment with another CRF 1 receptor antagonist CP-154,526 (10 mg/kg systemically) during the first and second withdrawals also counteracted anxiety-like behavior. These findings indicate that the CRF system and CRF 1 receptors play key roles in the adaptive change responsible for the anxiety-like behavior induced by repeated withdrawals from chronic ethanol.

show abstract

“…Conversely, GABA A receptor antagonists (Allan and Harris, 1987;Brouillet et al, 1991) and BZD-receptor inverse agonists (Mehta and Ticku, 1989;Becker and Anton, 1989) exacerbated seizure susceptibility associated with ethanol withdrawal. Withdrawal from chronic ethanol also results in an anxiety-like response (File et al, 1989;Criswell and Breese, 1989)Fa response blocked by BZDs and GABAmimetic drugs (Cooper et al, 1979;Criswell and Breese, 1989). Additionally, flumazenil, a BZD-receptor antagonist, blocked the anxiogenic consequence of ethanol withdrawal (File et al, 1989;Breese, 1990, 1993).…”

Section: Interaction Of Ethanol With the Gaba System In Vivomentioning

confidence: 99%

“…Withdrawal from chronic ethanol also results in an anxiety-like response (File et al, 1989;Criswell and Breese, 1989)Fa response blocked by BZDs and GABAmimetic drugs (Cooper et al, 1979;Criswell and Breese, 1989). Additionally, flumazenil, a BZD-receptor antagonist, blocked the anxiogenic consequence of ethanol withdrawal (File et al, 1989;Breese, 1990, 1993).…”

Section: Interaction Of Ethanol With the Gaba System In Vivomentioning

confidence: 99%

A Conceptualization of Integrated Actions of Ethanol Contributing to its GABAmimetic Profile: A Commentary

Criswell

Breese

2005

Neuropsychopharmacol

View full text Add to dashboard Cite

Early behavioral investigations supported the contention that systemic ethanol displays a GABAmimetic profile. Microinjection of GABA agonists into brain and in vivo electrophysiological studies implicated a regionally specific action of ethanol on GABA function. While selectivity of ethanol to enhance the effect of GABA was initially attributed an effect on type-1-benzodiazepine (BZD)-GABA A receptors, a lack of ethanol's effect on GABA responsiveness from isolated neurons with this receptor subtype discounted this contention. Nonetheless, subsequent work identified GABA A receptor subtypes, with limited distribution in brain, sensitive to enhancement of GABA at relevant ethanol concentrations. In view of these data, it is hypothesized that the GABAmimetic profile for ethanol is due to activation of mechanisms associated with GABA function, distinct from a direct action on the majority of postsynaptic GABA A receptors. The primary action proposed to account for ethanol's regional specificity on GABA transmission is its ability to release GABA from some, but not all, presynaptic GABAergic terminals. As systemic administration of ethanol increases neuroactive steroids, which can enhance GABA responsiveness, this elevated level of neurosteroids is proposed to magnify the effect of GABA released by ethanol. Additional factors contributing to the degree to which ethanol interacts with GABA function include an involvement of GABA B and other receptors that influence ethanol-induced GABA release, an effect of phosphorylation on GABA responsiveness, and a regional reduction of glutamatergic tone. Thus, an integration of these consequences induced by ethanol is proposed to provide a logical basis for its in vivo GABAmimetic profile.

show abstract

Flumazenil but not nitrendipine reverses the increased anxiety during ethanol withdrawal in the rat

Cited by 110 publications

References 16 publications

Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis

Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis

Modulation of multiple ethanol withdrawal-induced anxiety-like behavior by CRF and CRF1 receptors

A Conceptualization of Integrated Actions of Ethanol Contributing to its GABAmimetic Profile: A Commentary

Contact Info

Product

Resources

About