Sex differences in responses of the basolateral-central amygdala circuit to alcohol, corticosterone and their interaction

Abstract

Alcohol use disorders are chronically relapsing conditions that pose significant health challenges for our society. Stress is a prevalent trigger of relapse, particularly for women, yet the mechanisms by which alcohol and stress interact, and how this differs between males and females, remain poorly understood. The glutamatergic circuit connecting the basolateral (BLA) and central (CeA) nuclei of the amygdala is a likely locus for such adaptations, yet the impact of alcohol, corticosterone and their interaction on this circuit has been understudied. In particular, no studies have addressed sex differences in these effects or potential differential responses between the lateral and medial subdivisions of the central nucleus. Thus, we assessed the effects of alcohol and corticosterone treatments on BLA-evoked compound glutamatergic responses in medial and lateral CeA neurons from male and female rats. We observed minimal differences between medial and lateral CeA responses to alcohol and corticosterone in male rats, which were primarily sensitive to alcohol-induced inhibition of glutamatergic postsynaptic potentials. Unlike male neurons, cells from female rats displayed reduced sensitivity to alcohol’s inhibitory effects. In addition, female neurons diverged in their sensitivity to corticosterone, with lateral CeA neuronal responses significantly blunted following corticosterone treatment and medial CeA neurons largely unchanged by corticosterone or subsequent co-application of alchol. Together these data highlight striking differences in how male and female amygdala respond to alcohol and the stress hormone corticosterone, factors which may impact differential susceptibility of the sexes to alcohol- and stress-related disorders.

Sex differences in binge‐like EtOH drinking, corticotropin‐releasing hormone and corticosterone: effects of β‐endorphin

“…Despite formidable evidence that women are more sensitive to stress, alcohol and their interaction (Logrip et al 2017), the neural mechanisms underlying sex-specific regulation of alcohol use have been poorly understood. The present findings help fill this gap by demonstrating sexually dimorphic neuropeptide regulation of EtOH sensitivity.…”

CRF modulates glutamate transmission in the central amygdala of naïve and ethanol-dependent rats

“…We examined paired-pulse facilitation (PPF) in each neuron using paired stimuli at 50 and 100 ms inter-stimulus interval (Andreasen and Hablitz, 1994; Logrip M., 2017; Roberto et al, 2004b). PPF was calculated as the amplitude of the second EPSP over that of the first EPSP.…”

Taurine Suppression of Central Amygdala GABAergic Inhibitory Signaling via Glycine Receptors Is Disrupted in Alcohol Dependence

“…The magnitude of the ratio is a measure of probability of release for stimulated neurons, such that PPR values above 1 indicate a relative low probability of release, whereas PPR below 1 indicates a relative high probability of release. Additionally, a drug‐induced change in PPR reflects presynaptic effects such that an increase in PPR suggests a decrease in neurotransmitter (GABA) release (Andreasen and Hablitz, ; Kirson et al, ; Logrip et al, ; Manabe et al, ).…”

“…These stimulus strengths were maintained throughout the duration of the experiment. We examined paired‐pulse ratio (PPR), whereby 2 stimuli of the same intensity are applied at varied interstimulus intervals (ISI; Andreasen and Hablitz, ; Kirson et al, ; Logrip et al, ; Manabe et al, ). PPR is calculated as the amplitude of the second eIPSP over that of the first eIPSP.…”