Sophia Khom

2 papers in the library · 12 citations · publishing 2021

Papers

Self-Administration of Entactogen Psychostimulants Dysregulates Gamma-Aminobutyric Acid (GABA) and Kappa Opioid Receptor Signaling in the Central Nucleus of the Amygdala of Female Wistar Rats

Frontiers in Behavioral Neuroscience December 16, 2021 Sophia Khom, Jacques D. Nguyen, Sophia A. Vandewater et al. 12 citations

Female rats that self-administer the entactogen psychostimulants methylone, pentylone, and MDMA escalate their drug intake under extended-access conditions, similar to male rats and typical psychostimulants. Pentylone and methylone led to more infusions than MDMA, and pentylone produced higher breakpoints in progressive ratio testing. In the central amygdala, baseline GABAergic inhibition was elevated after pentylone and MDMA self-administration: pentylone increased both GABA release and postsynaptic receptor function, while MDMA increased only postsynaptic function. Both drugs disrupted kappa opioid receptor signaling, with both agonist and antagonist decreasing GABA release, indicating non-canonical pathways. These findings suggest central amygdala GABA and kappa opioid mechanisms are critically involved in entactogen self-administration escalation.

DOI: 10.3389/fnbeh.2021.780500 Full text MDMA Intravenous self-administration Pentylone Methylone +2

Self-Administration of entactogen psychostimulants dysregulates GABA and Kappa Opioid Receptor signaling in the central nucleus of the amygdala of female Wistar rats

bioRxiv Preprint Server September 24, 2021 Sophia Khom, Jacques D. Nguyen, Sophia A. Vandewater et al. preprint

Female rats that self-administered the entactogen psychostimulants methylone, pentylone, or MDMA under extended-access conditions escalated their drug intake, with methylone and pentylone producing more infusions than MDMA. Pentylone also led to higher breakpoints in progressive-ratio testing, indicating greater motivation. At the cellular level, both pentylone and MDMA increased baseline GABA transmission in the central nucleus of the amygdala (CeA): pentylone raised both the frequency and amplitude of miniature inhibitory postsynaptic currents, while MDMA increased only amplitude. Both drugs disrupted kappa opioid receptor (KOR) signaling in the CeA, with both KOR agonism and antagonism reducing GABA release, suggesting recruitment of non-canonical pathways. These findings indicate that CeA GABA and KOR mechanisms are critically involved in entactogen self-administration, similar to patterns seen with alcohol and cocaine.

DOI: 10.1101/2021.09.24.461477 Full text