Article

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.

Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 08/1995; 15(8):5439-47.
Source: PubMed

ABSTRACT 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).(ABSTRACT TRUNCATED AT 250 WORDS)

0 Bookmarks
 · 
49 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Anxiety-like behaviors are integral features of withdrawal from chronic ethanol exposure. In the experiments in the current study, we tested the hypothesis that anxiety can be regulated independently of other withdrawal signs and thus may be responsive to selective pharmacological agents. For 17 days, rats were fed ethanol (8–12 g/kg/day) in a liquid diet. Between 5 and 6 h after cessation of ethanol treatment, rats were tested in either the social interaction or plus-maze test of anxiety-like behavior after treatment with drugs hypothesized to have anxiolytic action. SB242084, flumazenil, and CRA1000—antagonists for 5-hydroxytryptamine (serotonin) (5-HT) 2C (5-HT2C), benzodiazepine, and corticotropin-releasing factor type 1 (CRF1) receptors, respectively—attenuated decreased social interaction without concomitant effects on activity measures. In contrast, ifenprodil, MDL 72222, and zolpidem—antagonists for N-methyl-d-aspartate (NMDA) and 5-HT3 receptors, and agonist for benzodiazepine type 1 receptors, respectively—did not share this effect. Results for SB242084, flumazenil, and ifenprodil in the elevated plus-maze test were comparable to those in the social interaction test. These results support the suggestion that multiple neuronal systems (CRF1, 5-HT2C, and benzodiazepine receptors) contribute to the ethanol withdrawal sign of decreased social interaction. Furthermore, the selective effects of pharmacological agents on social interaction seem to indicate that this behavior can be dissociated from other signs. Because anxiety may be a complicating factor in alcohol withdrawal and relapse, future studies of this type are needed to provide focus for the effort to define selective and novel antianxiety agents for these disorders.
    Alcohol 02/2004; 32(2):101-111. DOI:10.1016/S0741-8329(04)00012-6 · 2.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The ability to respond to actual and perceived threats is critical to survival. Among the regulatory systems activated in such circumstances is the hypothalamic-pituitary-adrenal (HPA) axis. Adrenocortical secretion of glucocorticoids, which act to mobilize the body's energy resources and adjust metabolism in order to optimize survival, represents the final step in a neuroen-docrine cascade beginning in the central nervous sys-tem (CNS). Somatic and psychological stressors, circa-dian drive, and humoral influences initiate this cascade by releasing multiple adrenocorticotrophic hormone (ACTH) secretagogues of hypothalamic origin into the hypophysial-portal circulation. Information about the internal and external environment reaches these hypothalamic neurosecretory ceils over a diffuse and interconnected network that is, itself, glucocorticoid sensitive. The functional activity of the HPA axis is crit-ically dependent on glucocorticoid feedback processes acting at the hippocampus and other structures which serve to regulate basal levels, damp the stressor-induced activation of the HPA axis, and shut off further gluco-corticoid secretion. Together these mechanisms permit rapid adjustment of the HPA axis in response to the demands of the environment. In addition to their neg-ative feedback actions on the HPA axis, glucocorticoids play a major role in CNS maturational processes via their actions as transcriptional regulators of genes en-coding structural proteins, signaling cascade molecules, growth factors, and apoptotic cascades, implying that tight control over their production is of critical impor-tance for the harmonious development of the organ-ism. During prenatal and neonatal periods of brain de-velopment, exogenous and endogenous glucocorticoid exposure is capable of programming lifelong respon-siveness of stress-sensitive neurocircuits and may also modify learning and memory processes. The main-tenance of optimal concentrations of glucocorticoids during sensitive developmental periods is achieved through changes in adrenal sensitivity to ACTH and adaptive changes in HPA axis regulation. Nonetheless, in many species thus far evaluated, exposure to stres-sors such as abuse or neglect during sensitive periods of brain development in fetal or neonatal life leads to long-term physiological and behavioral consequences. In this chapter, the effects of glucocorticoids on the brain are discussed in relation to the ontogeny and regulation of the HPA axis and its associated neuro-circuitry. In addition, long-term consequences of fetal and neonatal stress are reviewed.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The central amygdala (CeA) plays a central role in physiological and behavioral responses to fearful stimuli, stressful stimuli, and drug-related stimuli. The CeA receives dense inputs from cortical regions, is the major output region of the amygdala, is primarily GABAergic (inhibitory), and expresses high levels of pro- and anti-stress peptides. The CeA is also a constituent region of a conceptual macrostructure called the extended amygdala that is recruited during the transition to alcohol dependence. In this review, we discuss neurotransmission in the CeA as a potential integrative hub between anxiety disorders and Alcohol Use Disorder (AUD), which are commonly co-occurring in humans. Human imaging work and multi-disciplinary work in animals collectively suggest that CeA structure and function are altered in individuals with anxiety disorders and AUD, the end result of which may be disinhibition of downstream “effector” regions that regulate anxiety- and alcohol-related behaviors.
    Biological Psychiatry 09/2014; DOI:10.1016/j.biopsych.2014.09.008 · 9.47 Impact Factor

Full-text (2 Sources)

Download
83 Downloads
Available from
May 27, 2014