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Kratom is derived from the leaves of a plant (Mitragyna speciosa) native to Southeast Asia that has been consumed for its complex stimulant-like effects at low doses, opiate-like effects at high doses, to treat mood related issues like anxiety or depression, or to help ameliorate opioid withdrawal symptoms. However, the neural mechanisms of its major psychoactive alkaloids, mitragynine (MG) and 7-hydroxymitragynine (7-HMG), are still not clear. Given that the effects of kratom are often compared to drugs with abuse liabilities, the current study examined the effects of MG and 7-HMG on reward-related neurotransmission. Fixed potential amperometry was used to quantify stimulation-evoked phasic dopamine release in the nucleus accumbens (NAc) of anesthetized male and female mice before and after MG (1, 15, or 30 mg/kg i.p.), 7-HMG (0.5, 1, or 2 mg/kg i.p.), or vehicle. MG reduced dopamine release over the recording period (90 min) in a dose dependent manner, and the low dose of MG significantly increased dopamine autoreceptor functioning in males. Both sexes responded similarly to 7-HMG with the low dose of 7-HMG increasing dopamine release while the high dose decreased dopamine release. 7-HMG did not alter dopamine autoreceptor functioning for either sex. Neither MG nor 7-HMG altered the clearance rate of stimulation-evoked dopamine. Findings suggest that these kratom alkaloids do alter dopamine functioning, although potentially not in a way consistent with classic drugs of abuse. Further investigation of the neural mechanisms of kratom’s alkaloids will provide crucial and urgent insight into their therapeutic uses or potential abuse liability.more » « lessFree, publicly-accessible full text available February 1, 2026
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Early life adversity (ELA) is associated with a multitude of neural and behavioral aberrations. To develop treatments to mitigate the effects of ELA, it is critical to determine which aspects of cognition are affected and when these disturbances manifest across the lifespan. Here, we tested the effects of maternal separation, an established rodent model of ELA, on punishment-driven risky decision-making longitudinally in both adolescence (25–55 days old) and adulthood (80–100 days old). Risk-taking was assessed with the Risky Decision-making Task, wherein rats choose between a small, safe reward and a large reward accompanied by an escalating risk of punishment (foot shock). We observed that rats exposed to maternal separation were more prone to risk-taking than controls during adolescence, and demonstrated reduced latency to make both risky and safe decisions. Interestingly, this augmented risk-taking was no longer evident in adulthood. Males and females displayed comparable levels of risk-taking during adolescence then diverged in adulthood, with adult males displaying a sharp increase in risk-taking. Finally, we observed that risk-taking changed across the lifespan in rats exposed to maternal separation, but not in control rats. Collectively, these data reveal that ELA engenders risk-taking in adolescence but not adulthood, and that sex differences in risky decision-making are not evident until adulthood. This has important implications for the development of both behavioral and biological treatments to improve decision-making during the vulnerable adolescent period.more » « lessFree, publicly-accessible full text available January 1, 2026
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With grant support from the Research Experience for Undergraduates (REU) program funded by the National Science Foundation (NSF) and the Awards to Stimulate and Support Undergraduate Research Experiences (ASSURE) program funded by the Department of Defense (DoD) Air Force Office of Scientific Research (AFOSR), we established a program intended to increase the number of underrepresented racial and ethnic minority (URM) and first-generation undergraduate students successfully applying to neuroscience and other STEM-related graduate programs. The Neuroscience Techniques and Research Training (NeuroSTART) Program aimed to increase the number of undergraduate students from the Memphis area involved in behavioral neuroscience research. In this two-semester program, students completed an empirical research project in a neuroscience lab, received individual mentoring from neuroscience faculty, became part of a STEM network, presented at research conferences, and attended specialized professional development seminars. In two cohorts of 15 students, 4 are PhD students in neuroscience-related programs or in medical school (27%), 4 are employed in neuroscience-related research facilities (27%), 3 are employed as clinical assistants (20%), and 1 is employed in the IT field (7%). The remaining three recently graduated and are planning a gap year prior to applying for admission to grad/medical school. The Memphis NeuroSTART program has provided valuable training to participants, making them competitive applicants for jobs in the health sciences and for admittance into graduate neuroscience programs. By providing this training to first-generation and URM students, the broader impact of this program was an increase in the diversity of the health sciences workforce, particularly those specializing in neuroscience-related research and treatment.more » « less
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Introduction: Impulsivity is a symptom of Attention-Deficit/Hyperactivity Disorder (ADHD) and variants in the Lphn3 (Adgrl3) gene [OMIM 616417] have been linked to ADHD. This project utilized a delay-discounting (DD) task to examine the impact of Lphn3 deletion in rats on impulsive choice. “Positive control” measures were also collected in Spontaneously Hypertensive Rats (SHRs), another animal model of ADHD. Methods: For Experiment I, rats were given the option to press one lever for a delayed reward of 3 food pellets or the other lever for an immediate reward of 1 pellet. Impulsive choice was measured as the tendency to discount the larger, delayed reward. We hypothesized that impulsive choice would be greater in the SHR and Lphn3 knockout (KO) rats relative to their control strains - Wistar-Kyoto (WKY) and Lphn3 wildtype (WT) rats, respectively. Results: The results did not completely support the hypothesis, as only the SHRs (but not the Lphn3 KO rats) demonstrated a decrease in the percent choice for the larger reward. Because subsequent trials did not begin until the end of the delay period regardless of which lever was selected, rats were required to wait for the next trial to start even if they picked the immediate lever. Experiment II examined whether the rate of reinforcement influenced impulsive choice by using a DD task that incorporated a 1 sec inter-trial interval (ITI) immediately after delivery of either the immediate (1 pellet) or delayed (3 pellet) reinforcer. The results of Experiment II found no difference in the percent choice for the larger reward between Lphn3 KO and WT rats, demonstrating reinforcement rate did not influence impulsive choice in Lphn3 KO rats. Discussion: Overall, there were impulsivity differences among the ADHD models, as SHRs exhibited deficits in impulsive choice, while the Lphn3 KO rats did not.more » « less
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