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CB1 and ethanol effects on glutamatergic transmission in the central amygdala of male and female msP and Wistar rats.
Addict Biol. 2018 03; 23(2):676-688.AB

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 are also involved in regulation of stress, and we previously demonstrated that cannabinoid receptor type 1 (CB1) activation decreases CeA GABAergic signaling and blocks ethanol enhancement of GABAergic signaling. Here, we sought to investigate the effects of CB1 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 CB1 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 CB1 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 endocannabinoid effects on CeA glutamatergic signaling.

Authors+Show Affiliations

Department of Neuroscience, The Scripps Research Institute, La Jolla, California, USA.Department of Neuroscience, The Scripps Research Institute, La Jolla, California, USA.Department of Neuroscience, The Scripps Research Institute, La Jolla, California, USA.School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.Department of Neuroscience, The Scripps Research Institute, La Jolla, California, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28656627

Citation

Kirson, Dean, et al. "CB1 and Ethanol Effects On Glutamatergic Transmission in the Central Amygdala of Male and Female msP and Wistar Rats." Addiction Biology, vol. 23, no. 2, 2018, pp. 676-688.
Kirson D, Oleata CS, Parsons LH, et al. CB1 and ethanol effects on glutamatergic transmission in the central amygdala of male and female msP and Wistar rats. Addict Biol. 2018;23(2):676-688.
Kirson, D., Oleata, C. S., Parsons, L. H., Ciccocioppo, R., & Roberto, M. (2018). CB1 and ethanol effects on glutamatergic transmission in the central amygdala of male and female msP and Wistar rats. Addiction Biology, 23(2), 676-688. https://doi.org/10.1111/adb.12525
Kirson D, et al. CB1 and Ethanol Effects On Glutamatergic Transmission in the Central Amygdala of Male and Female msP and Wistar Rats. Addict Biol. 2018;23(2):676-688. PubMed PMID: 28656627.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CB1 and ethanol effects on glutamatergic transmission in the central amygdala of male and female msP and Wistar rats. AU - Kirson,Dean, AU - Oleata,Christopher Shaun, AU - Parsons,Loren Howell, AU - Ciccocioppo,Roberto, AU - Roberto,Marisa, Y1 - 2017/06/28/ PY - 2017/04/17/received PY - 2017/05/02/accepted PY - 2017/6/29/pubmed PY - 2019/9/19/medline PY - 2017/6/29/entrez KW - CB1 KW - CeA KW - eCB KW - ethanol KW - glutamate SP - 676 EP - 688 JF - Addiction biology JO - Addict Biol VL - 23 IS - 2 N2 - 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 are also involved in regulation of stress, and we previously demonstrated that cannabinoid receptor type 1 (CB1) activation decreases CeA GABAergic signaling and blocks ethanol enhancement of GABAergic signaling. Here, we sought to investigate the effects of CB1 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 CB1 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 CB1 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 endocannabinoid effects on CeA glutamatergic signaling. SN - 1369-1600 UR - https://www.unboundmedicine.com/medline/citation/28656627/CB1_and_ethanol_effects_on_glutamatergic_transmission_in_the_central_amygdala_of_male_and_female_msP_and_Wistar_rats_ L2 - https://doi.org/10.1111/adb.12525 DB - PRIME DP - Unbound Medicine ER -