Microinjection of a corticotropin-releasing factor antagonist into the central nucleus of the amygdala reverses anxiogenic-like effects of ethanol withdrawal

Rassnick, Stefanie; Heinrichs, Stephen C.; Britton, Karen T.; Koob, George F.

doi:10.1016/0006-8993(93)91352-s

Cited by 387 publications

(302 citation statements)

References 52 publications

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“…For example, the present findings do not permit a conclusive statement about the brain region(s) that may participate in the modulation of social interaction behavior by the CRF system(s). Previous work demonstrated that the central amygdala was involved in the anxiety induced by withdrawal from a single episode of chronic ethanol (Koob et al, 1998;Menzaghi et al, 1994;Rassnick et al, 1993). Such work emphasizes that extrahypothalamic sites are likely critical to the sensitized anxiety-like behavior induced by repeated withdrawals.…”

Section: Discussionmentioning

confidence: 95%

“…Antagonists of corticotropin-releasing factor (CRF) have been reported to reduce anxiety-like behavior observed in ethanol-withdrawn rats (Koob et al, 1998;Rassnick et al, 1993) and attenuate foot shock-induced reinstatement of ethanol-seeking behavior (Le et al, 2000). While CRF, by driving the HPA axis, could be a key factor in the adaptive changes associated with chronic ethanol, a recent study demonstrated that adrenalectomy does not modulate foot shockinduced reinstatement of ethanol-seeking behavior (Le et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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

Overstreet

Knapp

Breese

2004

Pharmacology Biochemistry and Behavior

159

153

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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to multiple withdrawals from chronic ethanol exhibit a sensitization of anxiety-like behavior compared to animals withdrawn from treatment with an equal but continuous amount of ethanol.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.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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

Overstreet

Knapp

Breese

2004

Pharmacology Biochemistry and Behavior

159

153

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“…CRF function, outside of the hypothalamic-pituitaryadrenal (HPA) axis, also is activated during acute withdrawal from opiates and other drugs of dependence, including cocaine, alcohol, opiates, and tetrahydrocannabinol, and thus may mediate some of the motivational effects associated with acute abstinence (Heinrichs et al, 1995;Koob et al, 1994;Richter and Weiss, 1999;Rodriguez de Fonseca et al, 1997). For example, animals exposed to chronic cocaine and alcohol show significant anxiety-like responses following cessation of chronic drug administration, which are reversed with intracerebroventricular administration of a CRF antagonist (Rassnick et al, 1993;Sarnyai et al, 1995). Microinjections into the central nucleus of the amygdala of lower doses of the CRF antagonist also reversed the anxiogenic-like effects of alcohol withdrawal (Rassnick et al, 1993), and similar doses of the CRF antagonist injected into the amygdala were active in reversing opiate-induced conditioned place aversion (Heinrichs et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…For example, animals exposed to chronic cocaine and alcohol show significant anxiety-like responses following cessation of chronic drug administration, which are reversed with intracerebroventricular administration of a CRF antagonist (Rassnick et al, 1993;Sarnyai et al, 1995). Microinjections into the central nucleus of the amygdala of lower doses of the CRF antagonist also reversed the anxiogenic-like effects of alcohol withdrawal (Rassnick et al, 1993), and similar doses of the CRF antagonist injected into the amygdala were active in reversing opiate-induced conditioned place aversion (Heinrichs et al, 1995). Studies using in vivo microdialysis have shown that rats withdrawn from chronic alcohol, withdrawn from chronic cocaine, and precipitously withdrawn from chronic cannabinoids show increases in the release of CRF from the central nucleus of the amygdala (Cummings et al, 1983;Merlo-Pich et al, 1995;Rodriguez de Fonseca et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Buprenorphine and a CRF1 Antagonist Block the Acquisition of Opiate Withdrawal-Induced Conditioned Place Aversion in Rats

Stinus

Cador

Zorrilla

et al. 2004

Neuropsychopharmacol

130

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Conditioned place aversion in rats has face validity as a measure of the aversive stimulus effects of opiate withdrawal that reflects an important motivational component of opiate dependence. The purpose of the present study was to validate conditioned place aversion as sensitive to medications that will alleviate the aversive stimulus effects of opiate withdrawal in humans, and to extend this model to the exploration of the neuropharmacological basis of the motivational effects of opiate withdrawal. Male Sprague-Dawley rats were implanted with two subcutaneous morphine pellets and 5 days later began place conditioning training following subcutaneous administration of a low dose of naloxone. Animals were subjected to three pairings of a low dose of naloxone (15 mg/kg, s.c.) to one arm of a three-chambered place conditioning apparatus. Buprenorphine administered prior to each pairing dose-dependently blocked the place aversion produced by precipitated opiate withdrawal. A corticotropin-releasing factor-1 (CRF 1 ) receptor antagonist (antalarmin) also reversed the place aversion produced by precipitated opiate withdrawal. Antalarmin did not produce a place preference or place aversion by itself in morphine-dependent rats. No effect was observed with pretreatment of the dopamine partial agonist terguride or the selective serotonin reuptake inhibitor fluoxetine. Also, chronic pretreatment with acamprosate (a glutamate receptor modulator used to prevent relapse in alcohol dependence) did not alter naloxone-induced place aversion. Buprenorphine by itself in dependent rats produced a mild place preference at low doses and a mild place aversion at higher doses. These results suggest that buprenorphine blocks the aversive stimulus effects of precipitated opiate withdrawal in rats and provides some validity for the use of place conditioning as a measure that is sensitive to potential opiate-dependence medications. In addition, these results suggest that CRF 1 antagonists can block the aversive stimulus effects of opiate withdrawal and may be potential therapeutic targets for opiate dependence.

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“…Previous studies demonstrated that several brainstem structures are involved in ETX seizure initiation and propagation Riaz, 1994, 1995;Faingold et al, 1998;Yang et al, 2003;Long et al, 2007). The amygdala is a limbic structure, which has been implicated in the ETX syndrome, based on metabolic, enzymatic, focal microinjection, immediate early gene, and behavioral evidence (Clemmesen et al, 1988;Rassnick et al, 1993;Knapp and Crews, 1999). We recently observed that amygdala neurons are also critically involved in the neuronal network subserving AGS propagation during ETX, since ETX seizures can be blocked by focal microinjection into amygdala, and amygdala neurons fire intensely during the later behavioral phases of AGS (Feng et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

The effects of chronic ethanol administration on amygdala neuronal firing and ethanol withdrawal seizures

Feng

Faingold

2008

Neuropharmacology

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SummaryPhysical dependence on ethanol results in an ethanol withdrawal (ETX) syndrome including susceptibility to audiogenic seizures (AGS) in rodents after abrupt cessation of ethanol. Chronic ethanol administration and ETX induce functional changes of neurons in several brain regions, including the amygdala. Amygdala neurons are requisite elements of the neuronal network subserving AGS propagation during ETX induced by a subacute "binge" ethanol administration protocol. However, the effects of chronic ethanol administration on amygdala neuronal firing and ETX seizure behaviors are unknown. In the present study ethanol (5 g/kg) was administered intragastrically in Sprague-Dawley rats once daily for 28 days [chronic intermittent ethanol (CIE) protocol]. One week later the rats began receiving ethanol intragastrically 3 times daily for 4 days (binge protocol). Microwire electrodes were implanted prior to CIE or on the day after CIE ended day 29 to record extracellular action potentials in lateral amygdala (LAMG) neurons. The first dose of ethanol administered in the binge protocol following CIE treatment did not alter LAMG neuronal firing, which contrasts with firing suppression seen previously in the binge protocol alone. These data indicate that CIE induces neuroadaptive changes in the ETX network which reduce LAMG response to ethanol. LAMG neuronal responses to acoustic stimuli prior to AGS were significantly decreased during ETX as compared to those before ethanol treatment. LAMG neurons fired tonically throughout the tonic convulsions during AGS. CIE plus binge treatment resulted in a significantly greater mean seizure duration and a significantly elevated incidence of death than was seen previously with the binge protocol alone, indicating an elevated seizure severity following chronic ethanol administration.

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Microinjection of a corticotropin-releasing factor antagonist into the central nucleus of the amygdala reverses anxiogenic-like effects of ethanol withdrawal

Cited by 387 publications

References 52 publications

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

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

Buprenorphine and a CRF1 Antagonist Block the Acquisition of Opiate Withdrawal-Induced Conditioned Place Aversion in Rats

The effects of chronic ethanol administration on amygdala neuronal firing and ethanol withdrawal seizures

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