About

Karen K. Szumlinski is a Full Professor of Psychological and Brain Sciences at the University of California, Santa Barbara, with affiliations to the Neuroscience Research Institute and the Department of Molecular, Cellular and Developmental Biology. She earned her BSc in Psychology and MSc in Medical Sciences at McMaster University in Canada, followed by a second MSc and her PhD in the Center for Neuroscience and Neuropharmacology at Albany Medical College in New York. Her post-doctoral training was conducted at the Neuroscience Institute at the Medical University of South Carolina. Her research focuses on the biochemical mechanisms underlying changes in brain and behavior resulting from chronic exposure to drugs of abuse, particularly psychomotor stimulants and alcohol. Her work examines the role of postsynaptic scaffolding proteins regulating extracellular glutamate and glutamate receptor function in drug- and stress-induced alterations in brain and behavior. She employs various techniques, including transgenic mice, neuropharmacological approaches, and viral vectors, to study the effects of manipulating glutamate signaling on binge alcohol consumption, cocaine craving, and methamphetamine preference. Her laboratory also develops mouse models for oral methamphetamine and prescription opioid-taking to facilitate high-throughput genetic studies of drug abuse. Dr. Szumlinski has contributed significantly to understanding the neurobiological basis of addiction and neuropsychiatric disorders related to substance abuse. She is actively involved in collaborative projects within her department and with other research laboratories nationally and internationally. Her work is funded by the NIH and UCSB, and she serves on multiple editorial boards and professional societies, including the American College on Neuropsychopharmacology and the Society for Neuroscience.

Research topics

• Psychology
• Neuroscience
• Pharmacology
• Internal medicine
• Chemistry

Selected publications

• Inactivation of NMDAR and CaMKII signaling within the prelimbic cortex blocks incubated cocaine- and sucrose-craving

  Neuropsychopharmacology · 2026-01-08

  articleOpen accessSenior author

  The incubation of craving is a term coined to characterize the behavioral phenomenon wherein cue-elicited craving strengthens over a period of abstinence. Incubated cocaine-craving is mediated, at least in part, by increased glutamate release within the prelimbic cortex (PL). We hypothesized that this glutamate release stimulates NMDA-type glutamate receptors (NMDARs), leading to calcium-dependent activation of CaMKII signaling that drives incubated craving. To test this hypothesis, adult male and female Sprague-Dawley rats were trained to self-administer either intravenous cocaine or sucrose pellets (6 h/day × 10 days) and tested for cue-elicited cocaine- or sucrose-craving in early versus later (i.e., after incubation) withdrawal. Incubated cocaine-seeking was associated with increased CaMKII activity in the PL, but no change in NMDAR subunits. In contrast, incubated sucrose-craving was associated with many sex-dependent changes in both NMDAR subunit expression and CaMKII activation that were subregion-selective. An intra-PL infusion of the NMDA antagonist D-AP5 (2.5 or 7.5 µg/side) or the CaMKII inhibitor myr-AIP (10 pg/side) blocked both incubated cocaine- and sucrose-craving, with no effects detected in early withdrawal. Co-infusion of both D-AP5 and myr-AIP exerted a larger effect on incubated cocaine-craving than either antagonist alone. These data corroborate earlier evidence for distinct biochemical correlates within mPFC between incubated cocaine- and sucrose-craving and, for the first time, demonstrate that both NMDAR and CaMKII activation within the PL are common drivers of incubated craving of potential relevance to the design of anti-craving medications in the contexts of both drug and food reinforcers.

  PublisherOA PDFDOI

• Financial Incentives for Substance Abstinence: A Systematic Review and Meta-analysis

  Nicotine & Tobacco Research · 2025-02-19 · 1 citations

  reviewOpen access

  INTRODUCTION: Substance use disorder (SUD) increased by 45% globally in the past 10 years, representing one of the largest increases in risk factors for disease. Financial incentives (FI) are a promising tool to promote health behavior change, including substance abstinence. We aim to address a 10-year gap in the evidence and identify key characteristics for optimal treatment. AIMS AND METHODS: A meta-analysis of randomized controlled trials (RCTs) was undertaken per Cochrane guidelines and the PRISMA 2020 checklist. Medline, PsycINFO, and EMBASE were searched up to September 11, 2024. Included studies offered FI to substance users in exchange for substance abstinence compared to an alternative intervention control. The primary outcome extracted was substance abstinence at the latest follow-up. Secondary outcomes such as cost-effectiveness, adverse events, and motivational assessments were also extracted. The risk of bias was analyzed using the RoB 1 tool. RESULTS: Of 5042 studies identified, 246 were shortlisted for full-text review and included 39 RCTs (N = 27 845) for meta-analysis. SUD categories spanning nicotine (n = 30, odds ratios [OR] = 1.83; 95% CI = 1.65 to 2.03, p < .001), alcohol (n = 3, OR = 4.69, 95% CI = 1.59 to 13.86, p = .005), stimulants (n = 2, OR = 3.52; 95% CI = 0.36 to 34.18, p = .28), and polydrug (n = 2, OR = 3.11, 95% CI = 0.53 to 18.25, p = .21) were meta-analyzed for improving abstinence rates. Cannabis and opioid subgroups could not be meta-analyzed. Overall effectiveness was significant for FI improving substance abstinence rates (OR = 1.93, 95% CI = 1.66 to 2.24, p < .001) with continued significance through 12-month or longer follow-ups (OR = 1.78; 95% CI = 1.50 to 2.12, p < .001). CONCLUSIONS: Findings from this meta-analysis suggest that FI are an effective tool for increasing substance abstinence, particularly nicotine and alcohol; however, future research is recommended for other substances such as stimulants and opioids. IMPLICATIONS: This systematic review and meta-analysis exploring the use of FI for SUDs provides the first update on trends in this field since 2014 and the first meta-analysis since 2006. Notably, this review challenges the concerns of sustainability and effects on motivation which have withheld the clinical application of FI for SUDs.

  PublisherDOI

• Cross-Sensitization between Binge Eating and Binge Drinking in a Novel C57BL/6NJ Murine Model of Disease Comorbidity Requires PDE4B Activation

  Journal of Neuroscience · 2025-03-31 · 3 citations

  articleOpen accessSenior author

  There is a high rate of comorbidity between binge eating (BE) and binge drinking (BD) behaviors, suggesting a common neuropathology. Recently, phosphodiesterase 4B ( PDE4B ) was identified as a pleiotropic gene associated with comorbid alcohol use disorder (AUD) and anorexia nervosa with BE in a genome-wide association study, implicating PDE4B as a potential contributor to shared genetic risk between these disorders. Here, we developed a novel mouse model of comorbid BE and BD in C57BL/6NJ mice in which mice underwent 10 d of BE, followed by 10 d of BD. Females exhibited cross-sensitization from BE to BD, which was apparent on the first day of ethanol access, whereas cross-sensitization emerged in males over multiple trials of BD. Accordingly immunoblotting of the nucleus accumbens tissue indicated a female-selective increase in PDE4B protein expression that was apparent on both the first and last day of BD in mice with a prior BE history. Acute pretreatment with the selective PDE4B inhibitor A33 (1.0 mg/kg) reduced the expression of cross-sensitization to BD in females on Day 1, and this effect was maintained during a 5 d A33 treatment regimen. The 5 d A33 treatment regimen also reduced expression of cross-sensitization to BD that had emerged in males over repeated sessions. These results provide preclinical, functional validation of PDE4B as a driver of food–ethanol cross-sensitization in a novel model for BE and BD comorbidity and support PDE4B in the shared genetic risk for these behavioral pathologies and as a target for pharmacotherapeutic intervention in comorbid AUD and BE behaviors.

  PublisherOA PDFDOI

• Examination of age- and sex-related changes in protein expression within the hippocampus and prefrontal cortex during withdrawal from a subchronic history of binge-drinking in C57BL/6J mice

  Frontiers in Behavioral Neuroscience · 2025-07-14

  articleOpen accessSenior authorCorresponding

  Introduction: Early-onset binge-drinking and biological sex are critical risk factors for the development of cognitive decline and neurodegeneration associated with Alzheimer's disease and related dementias (ADRDs). Recently, we demonstrated that a prior history of binge-drinking during adolescence induces what appears to be latent (>6 months post-drinking) changes in the expression of glutamate receptors and neuropathology markers within brain regions governing working and spatial memory, many of which precede the manifestation of overt cognitive anomalies. Methods: To determine whether alcohol-induced changes in protein expression manifest within the hippocampus and prefrontal cortex at earlier times post-drinking, we conducted immunoblotting on tissue from mice with a subchronic history of binge-drinking (14 days of 2-h access to 10, 20 and 40% ethanol) during either adolescence or adulthood. Results: We previously reported that this binge-drinking regimen produces mild, age- and sex-selective, changes in working memory and spatial recall when behavior was assayed starting a 1 or 30 days withdrawal. Here, we provide evidence a subchronic binge-drinking history is sufficient to alter the expression of certain glutamate receptors and ADRD-related proteins during the first few months following drinking cessation. Further, these alcohol-induced protein changes are regionally specific and sex-selective. Discussion: The present results add to our growing understanding of the long-term consequences of adolescent-onset binge-drinking of potential relevance to understanding individual variability in the cognitive consequences of heavy drinking.

  PublisherOA PDFDOI

• The striatal heterogeneous nuclear ribonucleoprotein H1 mRNA targetome associated with methamphetamine administration and behavior

  Progress in Neuro-Psychopharmacology and Biological Psychiatry · 2025-12-24 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• AMPA/kainate receptor activation within the prelimbic cortex is necessary for incubated cocaine-craving

  Frontiers in Psychiatry · 2025-08-14 · 1 citations

  articleOpen accessSenior author

  Introduction: The incubation of craving is a behavioral phenomenon in which cue-elicited craving increases during a period of drug abstinence. Incubated cocaine-craving is associated with increased extracellular glutamate within the medial prefrontal cortex (mPFC) and this release, particularly within the prelimbic (PL) subregion, is necessary for incubated cocaine-craving. A potential candidate mediating these incubation-driving effects of glutamate release within the PL are alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Methods: To investigate the role of mPFC AMPA receptors (AMPARs) in incubated craving, male and female Sprague-Dawley rats were trained to self-administer cocaine for 6 h/day for 10 consecutive days. Either during early or later withdrawal, rats were infused intra-PL with the AMPA/kainate receptor antagonist NBQX (0 or 1 µg/0.5 µl per side), followed by 30-min tests for cue-induced responding. Immunoblotting was also conducted to relate the expression of incubated cocaine- and sucrose-craving to AMPAR subunit expression within mPFC subregions. Results: Intra-PL NBQX blocked incubated craving expressed in late, but not early, withdrawal. In contrast, an intra-PL NBQX infusion increased cue-induced cocaine-seeking in female rats tested in early withdrawal. No incubation-related changes in AMPAR subunit expression were detected within the PL or IL of rats of either sex and no estrus-associated changes in subunit expression were detected in female rats exhibiting incubated cocaine-craving. In contrast, elevated GluA1 expression was observed within the IL of male rats exhibiting an incubation of sucrose-craving. Discussion: Together, these findings indicate a necessary role for AMPAR/kainate receptors within the PL in driving incubated cocaine-craving and suggest that AMPAR/kainate receptors located within the IL may be involved also in sucrose-craving selectively in males.

  PublisherDOI

• Review for "Ethanol Increases Diffuse Amyloid Plaque Load and Impairs Memory in the 5xFAD Mouse Model of Alzheimer's Disease"

  2025-01-06

  peer-review1st authorCorresponding
  PublisherDOI

• AMPA receptor activation within the prelimbic cortex is necessary for incubated cocaine-craving

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-23 · 1 citations

  preprintOpen accessSenior authorCorresponding

  The incubation of craving is a behavioral phenomenon in which cue-elicited craving increases during a period of drug abstinence. Incubated cocaine-craving is associated with increased extracellular glutamate within the medial prefrontal cortex (mPFC) and this release, particularly within the prelimbic (PL) subregion, is necessary for incubated cocaine-craving. A potential candidate mediating these incubation-driving effects of glutamate release within the PL are alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). To investigate the role of mPFC AMPARs in incubated craving, male and female Sprague-Dawley rats were trained to self-administer cocaine for 6 h/day for 10 consecutive days. Either during early or later withdrawal, rats were infused intra-PL with the AMPAR antagonist NBQX (0 or 1 μg/0.5 μl per side), followed by 30-min tests for cue-reinforced responding. Immunoblotting was also conducted to relate the expression of incubated cocaine- and sucrose-craving to AMPAR subunit expression within mPFC subregions. Intra-PL NBQX blocked incubated craving expressed in late, but not early, withdrawal. No incubation-related changes in AMPAR subunit expression were detected within the PL or IL of rats of either sex and no estrus-associated changes in subunit expression were detected in female rats exhibiting incubated cocaine-craving. In contrast, elevated GluA1 expression was observed within the IL of male rats exhibiting an incubation of sucrose-craving. Together, these findings indicate a necessary role for AMPARs within the PL in driving incubated cocaine-craving and suggest that AMPARs located within the IL may be involved also in sucrose-craving selectively in males.

  PublisherOA PDFDOI

• Inhibiting NMDAR-CaMKII Signaling within the Prelimbic Cortex Blocks Incubated Cocaine-Craving in Rats (Abstract ID: 162973)

  Journal of Pharmacology and Experimental Therapeutics · 2025-03-01

  articleSenior author
  PublisherDOI

• Time to choose: impact of intertrial interval on selecting between methamphetamine and food reinforcement in male and female rats

  Psychopharmacology · 2025-02-08 · 5 citations

  articleOpen access

  RATIONALE: A central component of substance use disorder is the maladaptive choice of the drug over natural reinforcers. Compared to other drugs of abuse, methamphetamine (METH) choice has received limited study. OBJECTIVE: We sought to characterize the role of intertrial interval on METH choice behavior. METHODS: We examined the choice of METH versus food, across multiple METH doses (0.05-0.2 mg/kg/infusion), between male and female rats, employing a fixed ratio (FR1) reinforcement schedule with intertrial intervals (ITIs) of 20 and 600 s. Rats learned to lever-press for either the METH or the food reinforcer during separate, alternating training sessions. Rats then underwent choice testing, where both levers were presented for 25 discreet trials per session. Lastly, under a progressive ratio (PR) schedule, breakpoints for METH and food were assessed during separate, alternating sessions. RESULTS: METH choice was substantially higher when using the 20 s versus 600 s ITI. When the 20 s ITI was used, choice was dose- but not sex-dependent. When using the 600 s ITI, choice was influenced by dose and sex, with female rats in the higher dose group choosing METH more than other groups. PR breakpoints were higher for METH than for food, and this effect was more pronounced among female rats. METH choice was positively correlated with the ratio of METH/food breakpoints. CONCLUSION: Reinforcement schedule parameters, namely ITI, during discrete choice testing can markedly influence METH choice behavior; thus, this should be carefully considered during experiment design and selected based on overarching study aims.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01AA016650

  NIH · $1.7M · 2016

• NIH Grant R01DA024038

  NIH · $1.5M · 2013

• Adolescent Alcohol and Anxiety

  NIH · $1.7M · 2016–2022

Frequent coauthors

• Tod E. Kippin

  University of California, Santa Barbara

  69 shared

• Paul F. Worley

  Johns Hopkins Medicine

  45 shared

• Ilona Obara

  Newcastle University

  39 shared

• Joannalee C. Campbell

  37 shared

• Alexis W. Ary

  University of California, Santa Barbara

  37 shared

• George R. Uhl

  Universität Greifswald

  36 shared

• Nada Abdallah

  36 shared

• Michael J. Galsworthy

  36 shared

Awards & honors

• Fellow of the American College on Neuropsychopharmacology