About

Adriaan W Bruijnzeel joined the Department of Psychiatry at the College of Medicine, University of Florida, in 2004. He completed his doctorate in Neuropharmacology at Utrecht University in the Netherlands in 2001 and subsequently conducted a post-doctorate fellowship at the Scripps Research Institute in San Diego, California, where he studied the neuroadaptations underlying nicotine dependence. His work during this period was funded by the Tobacco-Related Disease Research Program of the State of California. Dr. Bruijnzeel's research focuses on neuropharmacology, with particular interest in addiction, nicotine dependence, and the interactions between opioids, cannabinoids, dopamine, and glucocorticoids in the context of pain, reward, and substance use disorders. He has contributed to the understanding of the neurobiological mechanisms underlying addiction and has been involved in various research projects related to lung cancer chemoprevention, opioid and cannabinoid interactions, and nicotine reinforcement. In addition to his research, Dr. Bruijnzeel is involved in teaching courses within the College of Medicine, including Introduction to Medical Science Seminar, Neuroscience Seminar, and Addiction: Neuroscience and Trends.

Research topics

• Psychology
• Medicine
• Internal medicine
• Psychiatry
• Anesthesia
• Chemistry
• Physiology
• Pharmacology
• Developmental psychology

Selected publications

• Progressive withdrawal-related reward deficits after nicotine self-administration in rats

  Nicotine & Tobacco Research · 2026-05-02

  articleSenior author

  INTRODUCTION: Tobacco use disorder is a chronic relapsing condition characterized by withdrawal symptoms following smoking cessation. Smoking cessation leads to anhedonia, which is a reduced ability to experience pleasure that contributes to relapse. To investigate the time course of withdrawal-related changes in reward function, we used intracranial self-stimulation (ICSS) to assess brain reward thresholds in rats during abstinence between intermittent long-access nicotine self-administration sessions. METHODS: Rats were implanted with ICSS electrodes to assess reward function and intravenous catheters for nicotine self-administration. Elevations in brain reward thresholds reflect decreased sensitivity to rewarding electrical stimuli, a preclinical measure of anhedonia-like behavior. Male rats self-administered 0.06 mg/kg of nicotine intermittently (three days per week, 23 h/day) for seven weeks. Brain reward thresholds were assessed at multiple time points between self-administration sessions during weeks 1-7. RESULTS: Elevations in thresholds were not observed during the first four weeks of nicotine self-administration. However, the brain reward thresholds were elevated in weeks 5 and 7, at least 12 h after nicotine self-administration, indicating progressive development of withdrawal-related alterations in reward function. The nicotinic receptor antagonist mecamylamine precipitated similar threshold elevations, supporting the development of nicotine dependence-related neuroadaptations. CONCLUSIONS: These findings indicate that changes in reward function consistent with anhedonia emerge gradually during the course of nicotine self-administration. Therefore, early behavioral or pharmacological interventions may help prevent the development of withdrawal-related anhedonia and reduce the risk of tobacco use disorder.

  PublisherDOI

• Assessing the Physiological Relevance of the Bioactivation of Tobacco Specific Carcinogen NNK and its Metabolite NNAL: Quantitative Analyses of Hydrolysis Products from Their Protein Adducts under Different Carcinogen Exposure Conditions

  Carcinogenesis · 2026-05-15

  article

  4-(Methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its major metabolite 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are tobacco-specific lung carcinogens. NNK is widely used in preclinical models to induce lung tumorigenesis for elucidating carcinogenesis mechanisms and developing preventive agents, because of the high tumor burden in a cost-effective manner. Typical NNK doses employed in these models substantially exceed levels in humans and the routes of administration (e.g., intraperitoneal injection, oral gavage, or delivery via drinking water) differ fundamentally from inhalational exposure through cigarette smoke. At the molecular level, NNK and NNAL undergo metabolic bioactivation by cytochrome P450 enzymes, generating reactive intermediates capable of covalently modifying DNA and proteins, thereby initiating carcinogenesis. NNK and NNAL are also subject to competing metabolism. Their portion undergoing carcinogenic bioactivation is expected to vary as a function of dose and route of exposure, raising concerns of physiological relevance of these preclinical models. Systematic comparison of NNK and NNAL bioactivation profiles in humans with these preclinical models can help assess their physiological relevance and inform translational application. Using LC-MS/MS methods, this study quantified 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB, an NNK-derived bioactivation hydrolysis product) and 1-(3-pyridyl)-1,4-butanediol (PBD, an NNAL-specific bioactivation hydrolysis product) in lung, liver and serum samples from two mouse models and in human lung and plasma samples. Marketed differences were observed between NNK intraperitoneal preclinical models and human samples; in contrast, the tobacco smoke-based preclinical model better recapitulates human NNK and NNAL bioactivation. These results provide guidance for the future use of these models in investigating lung carcinogenesis and developing preventive agents.

  PublisherDOI

• Cannabidiol reduces oxycodone self-administration while preserving its analgesic efficacy in a rat model of neuropathic pain

  Scientific Reports · 2026-01-11 · 1 citations

  articleOpen access1st authorCorresponding

  Prescription opioid misuse is a significant public health concern among individuals with chronic pain. Treating severe pain often requires high doses of opioids, increasing the risk of developing an opioid use disorder. Cannabidiol (CBD) is a non-intoxicating component of cannabis that has shown therapeutic potential without abuse liability. This study investigated the effects of CBD on oxycodone self-administration and hyperalgesia in an animal model of chronic neuropathic pain. Adult male rats were trained to self-administer intravenous oxycodone (0.06 mg/kg/infusion). Subsequently, they underwent chronic constriction injury (CCI) of the sciatic nerve or received sham surgery. Paw withdrawal latency was measured using the Hargreaves test as an indicator of thermal pain sensitivity. CBD (0, 1, 3, and 10 mg/kg, IP) was administered before the self-administration sessions, and pain testing was conducted afterward. The rats acquired oxycodone self-administration, as indicated by more active than inactive lever presses. CCI surgery decreased the paw withdrawal latency, confirming the induction of neuropathic pain. CCI alone did not affect oxycodone self-administration, suggesting that neuropathic pain does not substantially influence opioid intake at the dose tested. Treatment with CBD reduced oxycodone self-administration in both the sham and CCI rats. Oxycodone self-administration in the CCI rats reversed the CCI-induced decrease in paw withdrawal latency. However, CBD did not affect the antinociceptive effect of oxycodone in CCI rats. Taken together, these findings demonstrate that CBD reduces oxycodone self-administration without affecting the antinociceptive effects of oxycodone in neuropathic pain. This study supports the potential of CBD to reduce opioid use and misuse, regardless of pain status.

  PublisherOA PDFDOI

• Nicotine self-administration increases impulsive action: differential effects of nAChR modulators in a Go/No-Go task

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-02

  articleOpen accessSenior authorCorresponding

  Tobacco use disorder is a chronic condition characterized by compulsive nicotine use, withdrawal, and relapse following abstinence. Impulsivity contributes to persistent nicotine use and poor cessation outcomes. This study examined whether nicotinic acetylcholine receptor (nAChR) modulators alter impulsive action in a nicotine self-administration Go/No-Go task in male and female rats. Rats acquired intravenous nicotine self-administration and were then trained in a Go/No-Go procedure in which active lever presses were reinforced during Go periods but not during No-Go periods. We then assessed the effects of varenicline (0.1-3 mg/kg), nicotine (0.1-0.6 mg/kg), and the nAChR antagonist mecamylamine (0.5-2 mg/kg) in the Go/No-Go procedure. Varenicline and nicotine pretreatment reduced active responding during both Go and No-Go periods, whereas mecamylamine selectively reduced responding during No-Go periods. Mecamylamine decreased the percentage of active responses during No-Go trials, indicating reduced bias toward the nicotine-associated lever. In contrast, nicotine and varenicline did not alter response allocation, suggesting that their effects reflected nonspecific reductions in responding rather than changes in impulsive action. No sex differences were observed. Substituting saline for nicotine during self-administration did not alter active responding during Go periods, but rats in the saline group had fewer active responses during No-Go periods than rats in the nicotine group. These results show that chronic nicotine self-administration increases impulsive action and that nAChR antagonism, but not agonism or partial agonism, reduces nicotine-related impulsive action. This work supports the utility of the Go/No-Go self-administration task for investigating nAChR-dependent mechanisms underlying nicotine-induced impulsivity.

  PublisherDOI

• AB-free kava suppresses tobacco smoke-induced CREB phosphorylation in the mouse cerebellum

  Phytomedicine Plus · 2025-12-06

  articleOpen access

  • Tobacco smoke exposure consistently increased cAMP response element-binding protein (CREB) phosphorylation in mice cerebellum under different exposure regimens. • AB-free kava effectively suppressed tobacco smoke-induced p-CREB elevation in mice cerebellum. • The impact of AB-free kava suppression of tobacco smoke-induced p-CREB elevation remains to be determined. Our recent studies revealed the potential of AB-free kava as a novel therapeutic candidate against tobacco use disorder while the underlying mechanism remains to be elucidated. The cerebellum region in the brain has been reported to be involved in tobacco withdrawal. The cAMP response element-binding protein (CREB) activation via phosphorylation has also been reported to contribute to substance abuse, including tobacco use disorder. Our early pre-clinical work revealed the potential of AB-free kava to suppress tobacco smoke-induced CREB activation in lung tissues. In this study, we investigated the impact of tobacco smoke exposure on the levels of phosphorylated CREB (p-CREB) in the mouse cerebellum and evaluated the effects of AB-free kava. Four different regimens of tobacco smoke exposure consistently increased the levels of p-CREB in the cerebellum. AB-free kava effectively suppressed tobacco smoke-induced increase in p-CREB to levels comparable to mice without tobacco smoke exposure. Our data provide preliminary evidence that CREB activation in the cerebellum is a potential mechanism involved in tobacco use disorder and the protective potential of AB-free kava.

  PublisherDOI

• AB-Free Kava Suppresses Tobacco Smoke-Induced CREB Phosphorylation in the Mouse Cerebellum

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-18

  preprintOpen access

  Abstract Introduction Our recent studies revealed the potential of AB-free kava as a novel therapeutic candidate against tobacco use disorder while the underlying mechanism remains to be elucidated. The cerebellum region in the brain has recently been reported to be involved in tobacco smoke withdrawal. The cAMP response element-binding protein (CREB) activation via phosphorylation has also been reported to contribute to substance abuse, including tobacco use disorder. Our early pre-clinical work revealed the potential of AB-free kava to suppress tobacco smoke-induced CREB activation in lung tissues. Methods In this study, we investigated the impact of tobacco smoke exposure on the levels of phosphorylated CREB (p-CREB) in the mouse cerebellum and evaluated the effects of AB-free kava. Results Four different regimens of tobacco smoke exposure consistently increased the levels of p-CREB in the cerebellum. Importantly, AB-free kava effectively suppressed tobacco smoke-induced increase in p-CREB to levels comparable to mice without tobacco smoke exposure. Conclusions CREB activation in the cerebellum is a potential mechanism involved in tobacco use disorder, and our data provide preliminary evidence for the protective potential of AB-free kava.

  PublisherOA PDFDOI

• Cannabidiol Reduces Oxycodone Self-Administration While Preserving Its Analgesic Efficacy in a Rat Model of Neuropathic Pain

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-25

  preprintOpen access1st authorCorresponding

  Abstract Prescription opioid misuse is a significant public health concern among individuals with chronic pain. Treating severe pain often requires high doses of opioids, increasing the risk of developing an opioid use disorder. Cannabidiol (CBD) is a non-psychoactive component of cannabis that has shown therapeutic potential without abuse liability. This study investigated the effects of CBD on oxycodone self-administration and hyperalgesia in an animal model of chronic neuropathic pain. Adult male rats were trained to self-administer intravenous oxycodone (0.06 mg/kg/infusion). Subsequently, they underwent chronic constriction injury (CCI) of the sciatic nerve or received sham surgery. Paw withdrawal latency was measured using the Hargreaves test as an indicator of thermal pain sensitivity. CBD (0, 1, 3, and 10 mg/kg, IP) was administered before the self-administration sessions, and pain testing was conducted afterward. The rats acquired oxycodone self-administration, as indicated by more active than inactive lever presses. CCI surgery decreased the paw withdrawal latency, confirming the induction of neuropathic pain. CCI alone did not affect oxycodone self-administration, suggesting that neuropathic pain does not affect opioid intake. Treatment with CBD reduced oxycodone self-administration in both the sham and CCI rats. Oxycodone self-administration in the CCI rats reversed the CCI-induced decrease in paw withdrawal latency. However, CBD did not affect the antinociceptive effect of oxycodone in CCI rats. Taken together, these findings demonstrate that CBD reduces oxycodone self-administration without affecting the antinociceptive effects of oxycodone in neuropathic pain. This study supports the potential of CBD to reduce opioid use and misuse, regardless of pain status.

  PublisherOA PDFDOI

• TNF-α signaling mediates the dopaminergic effects of methamphetamine by stimulating dopamine transporters and L-type Ca ²⁺ channels

  Science Signaling · 2025-12-16 · 1 citations

  article

  The highly addictive psychostimulant methamphetamine increases the release of dopamine in the brain’s reward circuitry, where it also promotes the release of cytokines, including TNF-α, that contribute to neuroinflammation associated with methamphetamine abuse. Here, we found a dynamic interplay between methamphetamine and TNF-α in facilitating dopamine transmission within the ventral tegmental area (VTA) in mice. In ex vivo mouse brain slices and dopaminergic neurons, methamphetamine or TNF-α treatment increased dopamine release, intracellular Ca 2+ concentrations, and the firing activity of VTA dopaminergic neurons. These effects depended on the activity of dopamine transporter (DAT) and L-type voltage-gated Ca 2+ channels. Pharmacological inhibition of either DAT or TNF-α signaling mitigated these effects, suggesting that methamphetamine-induced alterations in VTA dopaminergic neurons are partially TNF-α dependent. These results underscore the role of neuroimmune signaling in modulating the dopaminergic circuitry and may inform therapeutic strategies for addressing methamphetamine addiction and its associated neuroinflammatory disorders.

  PublisherDOI

• Persistent Anhedonia After Intermittent Long-Access Nicotine Self-Administration in Rats

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-19

  preprintOpen accessSenior authorCorresponding

  Abstract Tobacco use disorder is a chronic condition characterized by compulsive nicotine use and withdrawal symptoms after smoking cessation. Smoking is the leading preventable cause of morbidity and mortality worldwide. Smoking cessation leads to anhedonia, which is an inability to experience pleasure from previously enjoyed activities and is caused by dysregulation of the brain’s reward and stress systems. It is also a key withdrawal symptom that contributes to relapse to smoking after a period of abstinence. To better understand the development of anhedonia, we investigated its onset and time course in rats that self-administered nicotine. Rats were implanted with intracranial self-stimulation (ICSS) electrodes to assess reward function and intravenous catheters for nicotine self-administration. Elevations in ICSS brain reward thresholds reflect decreased sensitivity to rewarding electrical stimuli, indicating anhedonia. The rats self-administered 0.06 mg/kg of nicotine intermittently, three days per week, for seven weeks. Brain reward thresholds were determined once a week 24 h after nicotine self-administration during weeks 1 to 3, and at 12, 24, and 48 h during weeks 4, 5, and 7. Elevations in brain reward thresholds were not observed during the first four weeks of nicotine self-administration. However, the brain reward thresholds were elevated in both weeks 5 and 7 at least 12 h after nicotine self-administration, indicating that anhedonia emerges gradually and then persists. As withdrawal severity gradually increases, smoking cessation may become more challenging. Therefore, behavioral or pharmacological interventions soon after smoking initiation are critical to prevent the development of a tobacco use disorder. Highlights Intermittent long-access nicotine self-administration leads to dependence in rats. Cessation of nicotine intake increased reward thresholds after 5 and 7 weeks. Anhedonia emerged after 5 weeks of long-access nicotine self-administration. Brain reward thresholds increased during spontaneous and precipitated withdrawal. Response latencies increased during both spontaneous and precipitated withdrawal.

  PublisherOA PDFDOI

• Cannabidiol interactions with oxycodone analgesia in an operant orofacial cutaneous thermal pain assay following oral administration in rats

  Pharmacology Biochemistry and Behavior · 2025-02-04 · 4 citations

  article
  PublisherDOI

Recent grants

• Tobacco: relationship between reduced nicotine content and reinforcement in rats

  NIH · $1.1M · 2016–2021

• NIH Grant R01DA023575

  NIH · $1.4M · 2015

• NIH Grant R03DA020504

  NIH · $143k · 2008

• Lasting behavioral and neuroimaging consequences of adolescent exposure to cannabis smoke.

  NIH · $410k · 2015–2018

• NIH Grant R03DA020502

  NIH · $147k · 2012

Frequent coauthors

• Marcelo Febo

  University of Florida

  32 shared

• Azin Behnood‐Rod

  University of Florida

  27 shared

• Ranjithkumar Chellian

  University of Florida

  24 shared

• V.M. Wiegant

  Leiden University Medical Center

  21 shared

• Rianne Stam

  National Institute for Public Health and the Environment

  19 shared

• Mark S. Gold

  17 shared

• Ryann Wilson

  University of Florida

  16 shared

• Barry Setlow

  Florida College

  16 shared

Education

• Ph.D., Neuropharmacology

  Utrecht University

  2001

• Other

  Scripps Research Institute