Abstract
Females are more likely to develop post-traumatic stress disorder (PTSD) than males. Also, symptoms of PTSD frequently precede alcohol abuse in females. Stressful, threat-related stimuli are evaluated by the amygdala, which is critical for establishing the emotional salience of environmental stimuli. Ethanol and stress have been shown to modify amygdala excitability, but effects of acute ethanol on neurons of the basolateral amygdala (BLA) in both males and females exposed to stress is unknown. The purpose of this study is to determine stress-induced changes in membrane properties of BLA neurons and to determine how ethanol modulates these changes in male and female rats. Whole-cell recordings were obtained from BLA neurons of both male and female rats exposed to single-prolonged stress (SPS). Neuronal excitability, quantified as the number of action potentials, was determined in current clamp mode by applying a series of depolarizing current steps. Hyperpolarization-activated current (Ih) was elicited in voltage clamp. Excitability and Ih amplitude were determined before and during the superfusion of ethanol (EtOH; 30 mM) in BLA neurons from SPS-treated male and female rats. SPS alone did not alter the firing properties of BLA neurons from either males or females. However, following SPS, BLA neurons from males and females respond differently to ethanol. Superfusion of EtOH (30 mM) inhibited spike firing in BLA neurons from rats exposed to SPS, and EtOH-induced inhibition was greater in females than in males exposed to stress. Also, EtOH (30 mM) selectively decreased Ih amplitude in BLA neurons from SPS-treated male rats from 171 ± 46 pA in (pre-EtOH) control to 53 ± 51 pA in the presence of EtOH (30 mM). EtOH did not reduce Ih in BLA neurons from SPS-treated females. Together, these suggest important sex differences in the physiological responses to EtOH in stress disorders such as PTSD, that have high comorbidity with alcohol use disorders.
Highlights
Post-traumatic stress disorder (PTSD) is a major public health concern
Single-prolonged stress produced no changes in resting membrane potential (RMP), input resistance (Rin), or the membrane time constant (Table 1)
We suggest that the anxiolytic properties of ethanol may involve the inhibition of excitability and in Hyperpolarization-Activated Current (Ih) in basolateral amygdala (BLA) neurons in male rats, but ethanol may be less anxiolytic in females because the inhibitory effect of ethanol on Ih is occluded by the low amplitude Ih observed in BLA neurons of females
Summary
Post-traumatic stress disorder (PTSD) is a major public health concern. PTSD typically develops after exposure to potentially life-threatening events such as sexual assault, natural disasters, or combat exposure (DiMauro et al, 2014). Specific populations are at higher risk of developing PTSD based on greater likelihood to experience trauma. Females are more likely to develop PTSD. Development of PTSD more frequently precedes alcohol dependence in women than in men (Sonne et al, 2003). Women with PTSD and alcohol use disorders (AUDs) are more likely to consume alcohol to alleviate symptoms of stress and anxiety (Lehavot et al, 2014). It is important to elucidate the cellular mechanisms that contribute to the roles of stress and anxiety that predispose to alcohol abuse
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