The Journal of pharmacology and experimental therapeutics
May 1, 2025
Amaya R Jenkins, Daniela B Radl, Thomas J Kornecook et al.
8 citations
Ketamine produces short-lived increases in reward responsiveness in rats under nonstressful conditions, but under ongoing chronic stress it rescues blunted reward responsiveness for nearly one week. These findings highlight the role of environmental context in ketamine's effects on reward processing and suggest its antianhedonic action may contribute to its antidepressant efficacy.
The International Journal of Neuropsychopharmacology
April 26, 2021
Alison Wakeford, Alexander M. Sherwood, Thomas E. Prisinzano et al.
6 citations
Synthetic cathinones produce behavioral effects similar to either psychostimulants like methamphetamine or entactogens like MDMA, depending on their dopaminergic or serotonergic activity. In squirrel monkeys trained to distinguish methamphetamine or MDMA from a placebo, cathinones such as MDPV, α-PVP, and methcathinone fully substituted for methamphetamine but only partially for MDMA, indicating primarily dopamine-mediated effects. Conversely, mephedrone and methylone fully substituted for MDMA but not for methamphetamine, suggesting a primary role for serotonin. These differences in interoceptive effects in nonhuman primates may reflect the subjective effects these drugs produce in humans.
British journal of pharmacology
November 1, 2025
Yasaman Razavi, Stephen J Kohut, Jack Bergman et al.
1 citation
Adolescent monkeys exposed daily to the cannabis compound Δ9-THC for six months, then tested about a year later as adults on a touchscreen attention task, required higher acute doses of Δ9-THC to impair their performance compared with animals that had not been exposed during adolescence. The impairment itself was dose-related and occurred whether the drug was given by injection or orally, though potency and timing differed. These results suggest that heavy cannabis use during adolescence can produce a lasting tolerance that persists into adulthood, even after a long period of abstinence.
July 9, 2018
Chu Hsien Lim, Brian D. Kangas, Jack Bergman
1 citation
Cancer patients face elevated rates of depression and anxiety, often leading to worse healthcare outcomes. Given limited treatment options, interest has grown in using psychedelics like psilocybin to manage these complications. Recent studies have shown the potential of psilocybin to alleviate depression and anxiety in cancer patients.
Neuropsychopharmacology
July 10, 2026
Christopher W. Thomas, Kayleigh S. Lamalfa, Tobias P. Whelan et al.
Psilocybin and ketamine acutely increased reward responsiveness in rats, and the effect persisted 24 hours after dosing. The increase from psilocybin, but not ketamine, was blocked by a 5-HT2A receptor antagonist. Other psychedelics, DMT and DOI, also acutely increased reward responsiveness but the effect did not last 24 hours. The non-psychedelic 5-HT2A agonist lisuride and the SSRI fluoxetine had no positive effects. These results suggest psychedelics can produce acute and enduring increases in reward responsiveness, partly through the 5-HT2A receptor, though the time course varies and clinical implications require further validation.
bioRxiv : the preprint server for biology
January 24, 2026
Kwang-Hyun Hur, Lisa D Nickerson, Jack Bergman et al.
THC, the psychoactive compound in cannabis, selectively amplifies behavioral and brain responses to cues that predict rewards, without affecting responses to neutral cues or baseline reward consumption. In squirrel monkeys, a low dose of THC (3 μg/kg) increased conditioned approach behavior toward a visual stimulus associated with food delivery. Functional MRI showed that THC enhanced activity in reward-related brain regions—anterior cingulate cortex, striatum, hippocampus, and substantia nigra-ventral tegmental area (SN-VTA)—while leaving visual and motor cortices unaffected. Resting-state connectivity analyses revealed that THC strengthened communication within mesocorticolimbic networks, with the SN-VTA acting as a central hub. These findings indicate that THC boosts incentive salience and motivational drive toward reward-associated stimuli through selective modulation of this circuitry.
Biological psychiatry global open science
July 1, 2025
Yalin Sun, Meenalochani Sivasubramanian, Marija Milenkovic et al.
Adolescent cannabis use increases risk for neuropsychiatric disorders, possibly through amygdala dysfunction. Chronic THC treatment in male adolescent nonhuman primates and rats disrupted sleep and increased anxiety-related behavior. THC activated proinflammatory glial cells (astrocytes) exclusively in the adolescent amygdala, upregulating GFAP and complement factor-B, effects absent in adults or other brain regions. THC also reduced synaptic plasticity markers stathmin-1 and NrCAM. Co-administered cannabidiol prevented astrocyte inflammation but did not restore plasticity markers. Astrogliosis correlated with fragmented sleep, attenuated plasticity markers with anxiety. Elevated CB1R expression in the maturing brain was astrocyte-localized in the amygdala, linking THC to unique adolescent amygdala vulnerability.