Biology subjects

Bruijnzeel, A.

Publications and source records attributed to Bruijnzeel, A..

6 recordsLinked to original sources

bioRxiv2024

The Role of Glucocorticoid and Nicotinic Acetylcholine Receptors in the Reward-Enhancing Effects of Nicotine in the ICSS Procedure in Male and Female Rats

Tobacco use disorder is a chronic disorder that affects more than one billion people worldwide and causes the death of millions each year. The rewarding properties of nicotine are critical for the initiation of smoking. Previous research has shown that the activation of glucocorticoid receptors (GRs) plays a role in nicotine self-administration in rats. However, the role of GRs in the acute rewarding effects of nicotine are unknown. In this study, we investigated the effects of the GR antagonist mifepristone and the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine on the reward-enhancing effects of nicotine using the intracranial self-stimulation (ICSS) procedure in adult male and female rats. The rats were prepared with ICSS electrodes in the medial forebrain bundle and then trained on the ICSS procedure. Nicotine lowered the brain reward thresholds and decreased response latencies similarly in male and female rats. These findings suggest that nicotine enhances the rewarding effects of ICSS and has stimulant properties. Treatment with the GR antagonist mifepristone did not affect the reward-enhancing effects of nicotine but increased response latencies, suggesting a sedative effect. Mecamylamine did not affect the brain reward thresholds or response latencies of the control rats, but prevented the nicotine-induced decrease in brain reward thresholds and reward latencies. These findings indicate that the rewarding effects of nicotine are mediated via the activation of nAChRs, and that the activation of GRs does not contribute to the acute rewarding effects of nicotine. These studies enhance our understanding of the neurobiological mechanisms underlying tobacco use disorder.

neuroscience↗

bioRxiv2024

AB-free kava enhances resilience against the adverse health effects of tobacco smoke in mice

Tobacco smoke remains a serious global issue, resulting in serious health complications, contributing to the onsets of numerous preventive diseases, and imposing significant financial burdens. Despite regulatory policies and cessation measures aimed at curbing its usage, novel interventions are urgently needed for effective damage reduction. Our preclinical and pilot clinical studies showed that AB-free kava has the potential to reduce tobacco smoke-induced lung cancer risk, mitigate tobacco dependence, and reduce tobacco use. To understand the scope of its benefits in damage reduction and potential limitations, this study evaluated the effects of AB-free kava on a panel of health indicators in mice exposed to 2 - 4 weeks of daily tobacco smoke exposure. Our comprehensive assessments included global transcriptional profiling of the lung and liver tissues, analysis of lung inflammation, evaluation of lung function, exploration of tobacco nicotine withdrawal, and characterization of the causal PKA signaling pathway. As expected, Tobacco smoke exposure perturbed a wide range of biological processes and compromised multiple functions in mice. Remarkably, AB-free kava demonstrated the ability to globally mitigate tobacco smoke-induced deficits at the molecular and functional levels with promising safety profiles, offering a unique promise to mitigate tobacco smoke-related health damages. Further pre-clinical evaluation and clinical translation are warranted to fully harness the potential of AB-free kava in combating tobacco smoke-related harms. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/599576v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1f6ee4corg.highwire.dtl.DTLVardef@96e062org.highwire.dtl.DTLVardef@16579a0org.highwire.dtl.DTLVardef@1140a8e_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2023

Maturational Differences in Affective Behaviors Involves Changes in Frontal Cortical-Hippocampal Functional Connectivity and Metabolomic Profiles

The differential expression of emotional reactivity from early to late adulthood may involve maturation of prefrontal cortical responses to negative valence stimuli. In mice, age-related changes in affective behaviors have been reported, but the functional neural circuitry warrants further investigation. We assessed age variations in affective behaviors and functional connectivity in male and female C57BL6/J mice. Mice aged 10, 30 and 60 weeks (wo) were tested over 8 weeks for open field activity, sucrose preference, social interactions, fear conditioning, and functional neuroimaging. Prefrontal cortical and hippocampal tissues were excised for metabolomics. Our results indicate that young and old mice differ significantly in affective behavioral, functional connectome and prefrontal cortical-hippocampal metabolome. Young mice show a greater responsivity to novel environmental and social stimuli compared to older mice. Conversely, late middle-aged mice (60wo group) display variable patterns of fear conditioning and with re-testing with a modified context. Functional connectivity between a temporal cortical/auditory cortex network and subregions of the anterior cingulate cortex and ventral hippocampus, and a greater network modularity and assortative mixing of nodes was stronger in young versus older adult mice. Metabolome analyses identified differences in several essential amino acids between 10wo mice and the other age groups. The results support differential expression of emotionality across distinct stages of the mouse lifespan involving greater prefrontal-hippocampal connectivity and neurochemistry.

neuroscience↗

bioRxiv2023

Mifepristone decreases nicotine intake in dependent and non-dependent adult rats

Addiction to tobacco and nicotine products has adverse health effects and afflicts more than a billion people worldwide. Therefore, there is an urgent need for new treatments to reduce tobacco and nicotine use. Glucocorticoid receptor blockade shows promise as a novel treatment for drug abuse and stress-related disorders. The aim of these studies was to investigate if glucocorticoid receptor blockade with mifepristone diminishes the reinforcing properties of nicotine in rats with intermittent or daily long access to nicotine. The rats self-administered 0.06 mg/kg/inf of nicotine for 6 h per day, with either intermittent (3 days per week) or daily access (7 days per week) for 4 weeks before treatment with mifepristone. Daily nicotine self-administration models regular smoking, while intermittent nicotine self-administration models occasional smoking. To determine if the rats were dependent, they were treated with the nicotinic acetylcholine receptor antagonist mecamylamine, and somatic signs were recorded. The rats with intermittent access to nicotine had a higher level of nicotine intake per session than those with daily access, but only the rats with daily access to nicotine showed signs of dependence. Furthermore, mecamylamine increased nicotine intake during the first hour of access in rats with daily access but not in those with intermittent access. Mifepristone decreased total nicotine intake in rats with intermittent and daily access to nicotine. Moreover, mifepristone decreased the total distance traveled and rearing in the open field test and operant responding for food pellets. These findings indicate that mifepristone decreases the reinforcing effects of nicotine and food, but it might also be somewhat sedative.

pharmacology and toxicology↗

bioRxiv2022

Dopamine D1-like receptor blockade and stimulation decreases operant responding for nicotine and food in male and female rats

Dopamine has been implicated in smoking, but there remains a need for a better understanding of the effects of dopamine D1-like receptor agonists on nicotine intake and the role of sex in the effects of dopaminergic drugs on nicotine intake. This work studied the effects of D1-like receptor stimulation and blockade on operant responding for nicotine and food and locomotor activity in male and female rats. The effects of the D1-like receptor antagonist SCH 23390 (0.003, 0.01, 0.03 mg/kg) and the D1-like receptor agonist A77636 (0.1, 0.3, 1 mg/kg) on responding for nicotine and food, and locomotor activity were investigated. The effects of SCH 23390 were investigated 15 min and 24 h after treatment, and the effects of the long-acting drug A77636 were investigated 15 min, 24 h, and 48 h later. Operant responding for nicotine and food was decreased 15 min, but not 24 h, after treatment with SCH 23390. Operant responding for nicotine was decreased 15 min, 24 h, and 48 h after treatment with A77636, and food responding was decreased 15 min and 24 h later. Locomotor activity was decreased 15 min, but not 24 h, after treatment with SCH 23390. A77636 only decreased locomotor activity 48 h after treatment. There were no sex differences in the effects of SCH 23390 or A77636. In conclusions, the D1-like receptor antagonist SCH 23390 reduces nicotine intake and causes sedation in rats. Stimulation of D1-like receptors with A77636 decreases nicotine intake at time points that the drug is not sedative.

pharmacology and toxicology↗

bioRxiv2021

Oxycodone decreases anxiety-like behavior in the elevated plus-maze test in male and female rats

The prescription opioid oxycodone is widely used for the treatment of pain in humans. Oxycodone misuse is more common among people with an anxiety disorder than those without one. Therefore, oxycodone might be misused for its anxiolytic properties. We investigated if oxycodone affects anxiety-like behavior in adult male and female rats. The rats were treated with oxycodone (0.178, 0.32, 0.56, or 1 mg/kg), and anxiety-like behavior was investigated in the elevated plus-maze test. Immediately after the elevated plus-maze test, a small open field test was conducted to determine the effects of oxycodone on locomotor activity. In the elevated plus-maze test, oxycodone increased the percentage of time spent on the open arms, the percentage of open arm entries, time on the open arms, open arm entries, and the distance traveled. The males treated with vehicle had a lower percentage of open arm entries than the females treated with vehicle, and oxycodone treatment led to a greater increase in the percentage of open arm entries in the males than females. Furthermore, the females spent more time on the open arms, made more open arm entries, spent less time in the closed arms, and traveled a greater distance than the males. In the small open field test, treatment with oxycodone did not affect locomotor activity or rearing. Sex differences were observed; the females traveled a greater distance and displayed more rearing than the males. In conclusion, oxycodone decreases anxiety-like behavior in rats, and oxycodone has a greater anxiolytic-like effect in males than females.

pharmacology and toxicology↗