Factors influencing vulnerability to drug abuse in female rats
Director, Mouse Behavior Core, University of Minnesota
Associate Director, MnDrive Optogenetics Core, University of Minnesota
Undergraduate Institution and Major/Degree:
University of Minnesota , BS, Neuroscience, 1999
My primary area of interest is examining factors that underlie sex differences in cocaine self-administration and reinstatement of cocaine-seeking behavior after an abstinence period. One factor that has been identified that mediates cocaine-directed behavior in females is estrogen, and estrogen enhances cocaine self-administration and reinstatement in females, but not males. Using the reinstatement model, we have recently shown that estrogen can enhance the motivation to seek cocaine in the absence of any effects on learning stimulus-reward associations. Current ongoing studies are underway to determine the receptor selectivity of estrogen action by treating female OVX rats with estrogen agonists that are selective for alpha- or beta-receptor subtypes. Future studies will address the potential site of action of estrogen by injecting estrogen agonists or antagonists into specific sites in the brain that are associated with reward and motivation as it relates to drug self-administration and reinstatement.
A secondary interest of mine, which is a primary area of interest in our lab, is to identify factors that confer vulnerability to drug abuse. By selecting "high" and "low" responders for certain traits, we can assess the relative vulnerability for drug abuse in these animals by measuring their self-administration behavior during acquisition and maintenance phases of drug addiction, or by testing their propensity to reinstate cocaine seeking behavior after a period of abstinence. Using this methodology, I and others have found that animals that are highly impulsive will initiate cocaine self-administration to a greater degree than low impulsive animals. I have also found that animals that are high wheel runners are more likely to self-administer cocaine, and to reinstate cocaine-seeking behavior compared to animals with low preferences for wheel running.
- Benneyworth MA, Hearing MC, Asp AJ, Madayag A, Ingebretson AE, Schmidt CE, Silvis KA, Larson EB, Ebner SR, Thomas MJ. Synaptic depotentiation and mGluR5 activity in the nucleus accumbens drive cocaine-primed reinstatement of place preference. J Neurosci. 2019 Apr 4. pii: 3020-17.
- Tonn Eisinger KR, Larson EB, Boulware MI, Thomas MJ, Mermelstein PG. Membrane estrogen receptor signaling impacts the reward circuitry of the female brain to influence motivated behaviors. Steroids. 2018 May;133:53-59.
- Ozburn AR, Larson EB, Self D, McClung C. Cocaine self-administration behaviors in ClockΔ19 mice". Psychopharmacol. 2012;223:169-177.
- Larson EB, Graham DL, Arzaga RR, Buzin N, Webb J, Green TA, Bass CE, Neve RL, Terwilliger EF, Nestler EJ, Self DW. Over-expression of CREB in the nucleus accumbens shell increases cocaine reinforcement in self-administering rats. J. Neurosci. 2011;31:16447-16457. Also selected for evaluation and inclusion in the Faculty of 1000.
- Choi KH, Edwards S, Graham DL, Larson EB, Whisler KN, Simmons D, Friedman AK, Walsh JJ, Rahman Z, Monteggia LM, Eisch AJ, Neve RL, Nestler EJ, Han MH, Self DW.Reinforcement-related regulation of AMPA glutamate receptor subunits in the ventral tegmental area enhances motivation for cocaine. J. Neurosci. 2011;31:7927-7937.
- Larson EB, Akkentli F, Edwards S, Graham DL, Simmons DL, Alibhai IN, Nestler EJ, Self DW.Striatal regulation of ΔFosB, FosB, and cFos during cocaine self-administration and withdrawal. J. Neurochem. 2010;115:112-122.
- Graham DL, Krishnan V, Larson EB, Graham A, Edwards S, Bachtell RK, Simmons D, Gent LM, Berton O, Bolanos CA, DiLeone RJ, Parada LF, Nestler EJ, Self DW. Tropomyosin-related kinase B in the mesolimbic dopamine system: Region-specific effects on cocaine reward. Biol. Psychiat. 2008;65:696-701.
- Larson EB, Anker JJ, Gliddon LA, Fons KS, Carroll ME. Effects of estrogen and progesterone on the escalation of cocaine self-administration in female rats during extended access. Exp Clin Psychopharmacol. 2007;15:461-471.
- Anker JJ, Larson EB, Gliddon LA, Carroll ME. Effects of progesterone on the reinstatement of cocaine-seeking behavior in female rats. Exp Clin Psychopharmacol. 2007;15(5):472-480.
- Larson EB, Carroll ME. Estrogen receptor β, but not α, mediates estrogen’s effect on cocaine-induced reinstatement of extinguished cocaine-seeking behavior in ovariectomized female rats. Neuropsychopharmacology. 2007;32(6):1334-45.
- Larson EB, Carroll ME. Wheel running as a predictor of cocaine self-administration and reinstatement in female rats. Pharmacol Biochem Behav. 2005;82(3):590-600.
- Larson EB, Roth ME, Anker JJ, Carroll ME. Effect of short- vs. long-term estrogen on reinstatement of cocaine-seeking behavior in female rats. Pharmacol Biochem Behav. 2005;82(1):98-108.
Conferences Attended and Presentations:
- Society for Neuroscience (SFN) annual meeting - 2000, 2002, 2004
- College of Problems in Drug Dependence (CPDD) meeting - 2000, 2002, 2005
- International Study Group Investigating Drugs as Reinforcers (ISGIDAR) meeting - 2002, 2005
- Marilyn Carroll
- Martin Wessendorf
- Robert Elde
- Dorothy Hatsukami
- Paul Pentel
Courses Taken Beyond the Core Courses:
- PHCL 5110: Intro to Pharmacology
- CSPH 5401: Intro to Ethnopharmacology
- NSC 8207: Psychopharmacology Seminar
- NSC 5462: Neuroscience of Drug Abuse
- NSC 8222: Central Regulation of Autonomic Function
- NSC 8216: Autonomic and Neuroendocrine Systems (Journal Club)
- PUBH 5452: Biostatistics II
Graduate Level Minor:
- Supporting program (pharmacology, neuroendocrinology, and statistics)
- David Brown
- Marilyn Carroll - Advisor
- Bill Engeland - Chair
- Allen Levine
- Paul Mermelstein
Awards and Honors:
- NIDA Director's Travel Award (2000)
- Golden Key National Honor Society Award (1999)
- International Study Group Investigating Drugs as Reinforcers (ISGIDAR) member: 2003-present
- Society for Neuroscience (SFN) member: 2000-present
- Focus on Animal Contributions to Science (FACTS) - 1999-2001
- Hermantown ( Duluth ), MN
- Brain Awareness Week - 1999, 2002, 2004
- Exhibitor at the MN State Fair Brain Booth - 2000, 2002, 2004
- Science Fair Judge in Minneapolis Middle Schools - 2001