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.
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.
Neuropharmacology
June 1, 2019
Jacques D Nguyen, Yanabel Grant, Kevin M Creehan et al.
Combined Δ9-tetrahydrocannabinol (THC) and oxycodone produced additive pain-relieving effects while reducing opioid self-administration in rats. Male rats trained to self-administer oxycodone intravenously obtained fewer infusions after inhaling vaporized THC or receiving injected THC (0-10 mg/kg, i.p.) compared to vehicle. Follow-up tests showed dose-dependent reductions across different oxycodone doses, with an intact loading dose arguing against general behavioral suppression. In separate groups of male and female Wistar rats, tail withdrawal latency increased more after inhaled THC (50 mg/mL) plus oxycodone (100 mg/mL) than either alone; similar additive antinociception occurred with injected THC (5.0 mg/kg, i.p.) and oxycodone (2.0 mg/kg, s.c.). These additive effects suggest THC could enhance opioid therapeutic efficacy and reduce abuse.