CB ₁ and Ethanol Effects on Glutamatergic Transmission in the Central Amygdala of male and female msP and Wistar Rats

Abstract

The central amygdala (CeA) is involved in the processing of anxiety and stress, and plays a role in ethanol consumption. Chronic ethanol recruits stress systems in the CeA, leading to aversive withdrawal symptoms. Although primarily GABAergic, CeA contains glutamatergic afferents, and we have reported inhibitory effects of ethanol on locally evoked glutamatergic responses in CeA of Wistar and Marchigian Sardinian alcohol-preferring (msP) rats. Notably, msP rats display enhanced anxiety, stress, and alcohol drinking, simulating the alcohol dependent phenotype. Endocannabinoids (eCB) are also involved in regulation of stress, and we previously demonstrated that cannabinoid receptor type 1 (CB ₁) activation decreases CeA GABAergic signaling and blocks ethanol enhancement of GABAergic signaling. Here, we sought to investigate the effects of CB ₁ activation (WIN 55,212-2; Win) and antagonism (AM251) with and without acute ethanol on glutamatergic synapses in CeA of female and male Wistar and msP rats. Using intracellular sharp pipette electrophysiology, we examined the effects of CB ₁ compounds on locally evoked excitatory postsynaptic potentials (EPSPs) in CeA, and compared effects between strains, gender, and estrous cycle. Acute ethanol decreased EPSP amplitudes in Wistars, and in male but not female msPs. Win decreased EPSP amplitudes in msPs, and in male but not female Wistars. Combined application of Win and ethanol resulted in strain specific effects in female rats. We found no tonic CB ₁ signaling at glutamatergic synapses in CeA of any groups, and no interaction with ethanol. Collectively, these observations demonstrate sex-strain-specific differences in ethanol and eCB effects on CeA glutamatergic signaling.