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

Em, Pich; Lorang, M.; Yeganeh, Morteza Nouruzi; Fonseca, Fernando Rodrı́guez de; Raber, Jacob; Gf, Koob; Weiss, Friedbert

doi:10.1523/jneurosci.15-08-05439.1995

Cited by 522 publications

(185 citation statements)

References 68 publications

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confidence: 87%

“…Behavioral studies indicate that injection of GABAergic antagonists directly into the CeA decreases motivated responding for oral self-administration of ethanol in rats, whereas infusion of GABA agonists and benzodiazepines decreased anxiety (11,12). Thus, these studies suggest that GABAergic systems in the CeA play a major role in the acute reinforcing effects of ethanol (13) and in the anxiogenic response to ethanol withdrawal (14).There has been a continuing controversy over the ability of ethanol to enhance GABAergic neurotransmission [inhibitory postsynaptic potentials͞inhibitory postsynaptic currents (IPSP͞ Cs)] in CNS neurons under basal conditions in other brain regions (see . Therefore, we have investigated effects of acute ethanol on basic membrane properties and on inhibitory GABAergic transmission within the CeA in a slice preparation.…”

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confidence: 90%

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Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons

Roberto

Madamba

Moore

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

327

384

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We examined the interaction of ethanol with the ␥-aminobutyric acid (GABA)ergic system in neurons of slices of the rat central amygdala nucleus (CeA), a brain region thought to be critical for the reinforcing effects of ethanol. Brief superfusion of 11-66 mM ethanol significantly increased GABA type A (GABA A) receptormediated inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) in most CeA neurons, with a low apparent EC50 of 20 mM. Acute superfusion of 44 mM ethanol increased the amplitude of evoked GABAA IPSPs and IPSCs in 70% of CeA neurons. The ethanol enhancement of IPSPs and IPSCs occurred to a similar extent in the presence of the GABA type B (GABA B) receptor antagonist CGP 55845A, suggesting that this receptor is not involved in the ethanol effect on CeA neurons. Ethanol superfusion also decreased pairedpulse facilitation of evoked GABAA IPSPs and IPSCs and always increased the frequency and sometimes the amplitude of spontaneous miniature GABA A IPSCs as well as responses to local GABA application, indicating both presynaptic and postsynaptic sites of action for ethanol. Thus, the CeA is the first brain region to reveal, without conditional treatments such as GABAB antagonists, consistent, low-dose ethanol enhancement of GABAergic transmission at both pre-and postsynaptic sites. These findings add further support to the contention that the ethanol-GABA interaction in CeA plays an important role in the reinforcing effects of ethanol.alcohol ͉ GABA IPSP͞Cs ͉ paired-pulse facilitation ͉ miniature synaptic current ͉ electrophysiology T he amygdala formation is a complex of interconnected nuclei that has been implicated in various physiological functions such as attention (1), memory (1-4), emotion (5-7), and autonomic control (3). This complex has been linked to the motivational effects of drugs of abuse and alcoholism in particular (8).The ␥-aminobutyric acid (GABA)ergic system, particularly in the central amygdala nucleus (CeA), has been implicated in the expression of emotionality, including behavioral states of fear and anxiety, as well as states associated with consummatory responses (9). The CeA is considered to be crucial in mediating the behavioral effects of acute and chronic ethanol consumption (10, 11). Because stress reduction has long been considered to contribute to ethanol-seeking behavior in humans, researchers hypothesized that the CeA and its connections might be sites for a GABA-like action of ethanol to mediate ethanol reinforcement. Behavioral studies indicate that injection of GABAergic antagonists directly into the CeA decreases motivated responding for oral self-administration of ethanol in rats, whereas infusion of GABA agonists and benzodiazepines decreased anxiety (11,12). Thus, these studies suggest that GABAergic systems in the CeA play a major role in the acute reinforcing effects of ethanol (13) and in the anxiogenic response to ethanol withdrawal (14).There has been a continuing controversy over the ability of ethanol to enhance GABAergic neurotransmission [inhib...

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confidence: 87%

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confidence: 90%

Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons

Roberto

Madamba

Moore

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

327

384

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“…It is also important to note that a growing body of evidence implicates the corticotropin-releasing factor (CRF) systems in the amygdala in anxiety responses. In fact, enhanced CRF release in the amygdala represents a mechanism underlying the anxiogenic and aversive consequences of withdrawal (Menard and Treit, 1999;Merali et al, 1998;Wiersma et al, 1995) common to drugs of abuse such as nicotine and ethanol (Merlo Pich et al, 1995;Rivier, 1996).…”

Section: Neurobiology Of Nicotine Vs Ethanol Interactionsmentioning

confidence: 99%

Combined Exposure to Nicotine and Ethanol in Adolescent Mice Differentially Affects Anxiety Levels during Exposure, Short-Term, and Long-Term Withdrawal

Abreu‐Villaça

Nunes

Queiroz-Gomes

et al. 2007

Neuropsychopharmacol

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Smoking and consumption of alcoholic beverages are frequently associated during adolescence. This association could be explained by the cumulative behavioral effects of nicotine and ethanol, particularly those related to anxiety levels. However, despite epidemiological findings, there have been few animal studies of the basic neurobiology of the combined exposure in the adolescent brain. In the present work we assessed, through the use of the elevated plus maze, the short-and long-term anxiety effects of nicotine (NIC) and/or ethanol (ETOH) exposure during adolescence (from the 30th to the 45th postnatal day) in four groups of male and female C57BL/6 mice: (1) Concomitant NIC (nicotine free-base solution (50 mg/ml) in 2% saccharin to drink) and ETOH (ethanol solution (25%, 2 g/kg) i.p. injected every other day) exposure; (2) NIC exposure; (3) ETOH exposure; (4) Vehicle. C57BL/6 mice were selected, in spite of the fact that they present slower ethanol metabolism, because they readily consume nicotine in the concentration used in the present study. During exposure (45th postnatal day: PN45), our results indicated that ethanol was anxiolytic in adolescent mice and that nicotine reverted this effect. Short-term drug withdrawal (PN50) elicited sex-dependent effects: exposure to nicotine and/or ethanol was anxiogenic only for females. Although neither nicotine nor ethanol effects persisted up to 1 month postexposure (PN75), the coadministration elicited an anxiogenic response. In spite of the fact that generalizations based on the results from a single strain of mice are prone to shortcomings, our results suggest that the deficient response to the anxiolytic effects of ethanol in adolescents co-exposed to nicotine may drive higher ethanol consumption. Additionally, increased anxiety during long-term smoking and drinking withdrawal may facilitate relapse to drug use.

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“…The amygdala and "extended amygdala" (Alheid et al 1995) are brain regions presumed to play a key role in supporting withdrawal-induced anxiety-like behavior (Koob 2003b;Merlo Pich et al 1995;Rassnick et al 1993). In preliminary data, Knapp et al (2004a) reported that flumazenil acts in the amygdala to antagonize sensitization of multiple withdrawal-induced anxiety-associated behaviors.…”

Section: Future Directionsmentioning

confidence: 99%

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

2004

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Rationale-The rationale for proposing the "kindling"/stress hypothesis is to provide a conceptual basis for the insidious development and maintenance of alcohol abuse.Objective and results-An objective of the hypothesis is to emphasize how continued alcohol abuse is linked to progressive neural adaptation. Work has shown that repeated withdrawals from chronic low levels of alcohol sensitize ("kindle") anxiety-like behavior ("anxiety") in rats, a finding consistent with multiple withdrawal kindling of seizure activity. Additionally, stress substitutes for initial cycles of the multiple withdrawal protocol to sensitize withdrawal-induced anxiety, which is indicative that stress is capable of facilitating neuroadaptive processes related to withdrawal. The persistence of adaptation caused by stress and multiple withdrawals is revealed by the appearance of withdrawal-induced anxiety following a future re-exposure to a single 5-day period of alcohol. This persisting adaptation also permits stress to induce anxiety during a period of abstinence-a response not observed in animals without previous exposure to alcohol. Furthermore, stress interacts with repeated withdrawals to enhance voluntary alcohol drinking. Results of other preclinical and clinical studies reported in the literature are integrated with these investigations in support of the proposed hypothesis.Conclusions-The "kindling"/stress hypothesis is based on the premise that repeated withdrawals from cycles of chronic alcohol exposure contribute to a progressive development of persisting adaptive change that sensitizes withdrawal-induced anxiety and allows stress to evoke symptoms associated with negative affect during abstinence. Thus, these consequences of repeated withdrawals account for the evolution of major characteristics of alcoholism, which include worsened acute withdrawal symptoms and increased stress-induced negative affect during abstinence, both of which enhance the likelihood of relapse-and with relapse an inability to limit an abusive pattern of alcohol intake. The "kindling"/stress hypothesis provides a clear strategy for future studies to explore the advancing neural adaptation proposed to contribute to the pathogenesis of alcoholism.

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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

Cited by 522 publications

References 68 publications

Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons

Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons

Combined Exposure to Nicotine and Ethanol in Adolescent Mice Differentially Affects Anxiety Levels during Exposure, Short-Term, and Long-Term Withdrawal

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

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