Ethanol Augments GABAergic Transmission in the Central Amygdala via CRF1 Receptors

Abstract

The central amygdala (CeA) plays a role in the relationship among stress, corticotropin-releasing factor (CRF), and alcohol abuse. In whole-cell recordings, both CRF and ethanol enhanced gamma-aminobutyric acid-mediated (GABAergic) neurotransmission in CeA neurons from wild-type and CRF2 receptor knockout mice, but not CRF1 receptor knockout mice. CRF1 (but not CRF2) receptor antagonists blocked both CRF and ethanol effects in wild-type mice. These data indicate that CRF1 receptors mediate ethanol enhancement of GABAergic synaptic transmission in the CeA, and they suggest a cellular mechanism underlying involvement of CRF in ethanol's behavioral and motivational effects.

Microinjection of Naltrexone into the Central, but not the Basolateral, Amygdala Blocks the Anxiolytic Effects of Diazepam in the Plus Maze

“…These results suggest that the anxiolytic properties of ethanol in the elevated plus maze are not regulated by opioid receptor systems within CeA or BLA nuclei of the amygdala. This is surprising since ethanol increases GABA release, GABA A receptor function (Roberto et al, 2003), GABAergic neurotransmission (Nie et al, 2004), and c-fos expression in GABAergic neurons (Morales et al, 1998) in the CeA. These results are also somewhat discrepant with previous reports from this lab (Wilson et al, 2003); however, some important technical differences between the previous report and the current study warrant discussion.…”

“…Another potential problem is that ethanol is known to affect several neurotransmitter systems including GABA (Roberto et al, 2003), glutamate (Lovinger et al, 1989), neuroactive steroids (Sanna et al, 2004), and a variety of neuropeptides including opioids (de Gortari et al, 2000) and CRF (Nie et al, 2004). Therefore, even if opioid receptors modulate GABA A receptor function in the amygdala, the ability of ethanol to affect other neurotransmitter and neuromodulatory systems may be sufficient to circumvent any opioid receptor effects on GABA A receptor function localized selectively within the CeA or BLA.…”

“…This class of drugs enhances g aminobutyric acid (GABA) neurotransmission by binding to benzodiazepine receptors in the GABA A receptor complex and augmenting response to GABA (as reviewed by Wilson, 1996). Another drug that enhances GABA A receptor function is ethanol (Nie et al, 2004;Nestoros, 1980;Macdonald, 1995), a drug commonly abused by individuals suffering from depression and anxiety (for reviews, see Eckardt et al, 1998;Pohorecky, 1981). Both these drugs are known to be anxiolytic in humans and produce reductions in anxietylike behavior in several animal models of behavior (Wilson et al, 2004;Pellow et al, 1985;Eckardt et al, 1998).…”

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

“…Wan et al (1996) found that IPSCs from CA1 pyramidal cells were only sensitive to ethanol enhancement in the presence of a GABA B antagonist, providing a mechanism for the variability reported (see subsequent section on GABA B receptor influences). In another brain region, investigators (Nie et al, 2004;Roberto et al, 2003) reported that ethanol enhanced IPSCs from amygdaloid neurons.…”

“…Subsequently, Roberto et al (2003Roberto et al ( , 2004a provided evidence that ethanol enhanced the effect of stimulusinduced GABA-mediated IPSPs and mIPSCs from neurons in slices from the central nucleus of the amygdala and caused release of GABA into microdialysatesFclear evidence that ethanol could facilitate GABA release. This action of ethanol to release GABA can apparently be modified at presynaptic sites (see designation in Figure 4), by GABA B (Ariwodola and Weiner, 2004;Wan et al, 1996) and corticotrophin releasing factor (CRF; Nie et al, 2004) receptors. Additionally, other neurotransmitter receptors affected by ethanol can influence neural circuits that influence GABA transmission (Carta et al, 2003(Carta et al, , 2004; Figure 3 Effect of ethanol on neural rate from cerebellar Purkinje neurons.…”