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.
Psychopharmacology
November 15, 2025
Elisabetta Ciccocioppo, Sara Massetti, Marcus W Meinhardt et al.
Alcohol use disorder (AUD) is a major medical problem with limited treatments. (R)-ketamine, a form of the dissociative psychedelic with fewer dissociative and anesthetic effects than the racemic mixture, reduced alcohol consumption in female but not in male Marchigian Sardinian alcohol-preferring (msP) rats when given orally at doses of 10, 20, and 40 mg/kg in a two-bottle free choice 24-hour drinking paradigm. No effect was observed on alcohol self-administration. (R)-ketamine also attenuated the retrieval of alcohol-related memories in female but not in male rats. These results suggest (R)-ketamine attenuates alcohol-related behaviors in a sex-dependent manner, with females showing higher sensitivity, supporting clinical investigation in patients with AUD.
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.