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Center for the Translational Neuroscience of Alcohol (CTNA)
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Behavioral and Neural Mechanisms Underlying the Therapeutic Effects of Mavoglurant in AUD

Overview

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Our studies focus on how precise mechanisms of cortico-striatal circuit activity are altered during alcohol seeking and chronic alcohol-induced decision-making impairments and how the novel mGlu5 negative allosteric modulator mavoglurant modulates these dynamics. We have refined tests of habit-related decision-making, using the novel rodent version of the multi-stage decision-making task and other paradigms to assess cue-associated alcohol-seeking behaviors. Our methods can importantly dissociate habitual from goal-directed decision-making processes based on online trial-by-trial choices.

Activities

The proposed studies will investigate how pre-existing individual variation in reward sensitivity promotes habitual ethanol-seeking and cue-induced relapse in animal models. We will identify neural mechanisms of dopaminergic and glutamatergic dysfunction in corticostriatal circuits that underlie the vulnerability to habitual ethanol-seeking behavior and relapse. The goal of these animal studies is to provide a neurobiological basis for the determination and assessment of new targets for treatment of heavy drinking or alcoholism.

Relevant Publications

  1. Torregrossa MM, Corlett PR, Taylor JR. (2011). Aberrant learning and memory in addiction. Neurobiol Learn Mem. [Epub ahead of print] PubMed PMID: 21376820.
  2. Gourley SL, Lee AS, Howell JL, Pittenger C, Taylor JR. (2010) Dissociable regulation of instrumental action within mouse prefrontal cortex. Eur J Neurosci. 32(10):1726-34. PMID: 21044173.
  3. Löf E, Olausson P, Stomberg R, Taylor JR, Söderpalm B. (2010). Nicotinic acetylcholine receptors are required for the conditioned reinforcing properties of sucrose-associated cues. Psychopharmacology (Berl). 212(3):321-8. PMID: 20676610.
  4. Barker JM, Torregrossa MM, Arnold AP, Taylor JR. (2010). Dissociation of genetic and hormonal influences on sex differences in alcoholism-related behaviors. J Neurosci. 30(27):9140-4. PMID: 20610747.
  5. Gourley SL, Howell JL, Rios M, DiLeone RJ, Taylor JR. (2009). Prelimbic cortex bdnf knock-down reduces instrumental responding in extinction. Learn Mem. 16(12):756-60. PMID: 19926781.
  6. Potenza MN, Taylor JR. (2009). Found in translation: understanding impulsivity and related constructs through integrative preclinical and clinical research. Biol Psychiatry. 66(8):714-6. PMID: 19800484.
  7. Kimchi EY, Torregrossa MM, Taylor JR, Laubach M. (2009). Neuronal correlates of instrumental learning in the dorsal striatum. J Neurophysiol. 102(1):475-89. PMID: 19439679.
  8. Taylor JR, Olausson P, Quinn JJ, Torregrossa MM. (2009). Targeting extinction and reconsolidation mechanisms to combat the impact of drug cues on addiction. Neuropharmacology. 56 Suppl 1:186-95. PMID: 18708077.
  9. Torregrossa MM, Quinn JJ, Taylor JR. (2008). Impulsivity, compulsivity, and habit: the role of orbitofrontal cortex revisited. Biol Psychiatry. 63(3):253-5. PMID: 18194683.
  10. Becker JB, Monteggia LM, Perrot-Sinal TS, Romeo RD, Taylor JR, Yehuda R, Bale TL. (2007). Stress and disease: is being female a predisposing factor? J Neurosci. 27(44):11851-5. PMID: 17978023.
  11. Quinn JJ, Hitchcott PK, Umeda EA, Arnold AP, Taylor JR. (2007). Sex chromosome complement regulates habit formation. Nat Neurosci. 10(11):1398-400. PMID: 17952068.
  12. Löf E, Olausson P, deBejczy A, Stomberg R, McIntosh JM, Taylor JR, Söderpalm B. (2007). Nicotinic acetylcholine receptors in the ventral tegmental area mediate the dopamine activating and reinforcing properties of ethanol cues. Psychopharmacology (Berl). 195(3):333-43. PMID: 17703283.
  13. Hitchcott PK, Quinn JJ, Taylor JR. (2007). Bidirectional modulation of goal-directed actions by prefrontal cortical dopamine. Cereb Cortex. 17(12):2820-7. PMID: 17322558.
  14. Olausson P, Jentsch JD, Tronson N, Neve RL, Nestler EJ, Taylor JR. (2006). DeltaFosB in the nucleus accumbens regulates food-reinforced instrumental behavior and motivation. J Neurosci. 26(36):9196-204. PMID: 16957076.
  15. Lambe EK, Olausson P, Horst NK, Taylor JR, Aghajanian GK. (2005). Hypocretin and nicotine excite the same thalamocortical synapses in prefrontal cortex: correlation with improved attention in rat. J Neurosci. 25(21):5225-9. PMID: 15917462.