Toward early estimation and treatment of addiction vulnerability: radial arm maze and N-acetyl cysteine before cocaine sensitization or nicotine self-administration in neonatal ventral hippocampal lesion rats.

Autor: Rao KN; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA., Sentir AM; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.; IU Neuroscience Research Center, Indianapolis, IN, USA., Engleman EA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA., Bell RL; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA., Hulvershorn LA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.; Adolescent Dual Diagnosis Clinic, Riley Hospital for Children at IU Health, Indianapolis, IN, USA., Breier A; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Psychiatry, Psychotic Disorders Program at IU, Indiana University School of Medicine, Indiana University Prevention and Recovery Center for Early Psychosis (PARC), Indianapolis, IN, USA., Chambers RA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA. robchamb@iupui.edu.; IU Neuroscience Research Center, Indianapolis, IN, USA. robchamb@iupui.edu.; Laboratory for Translational Neuroscience of Dual Diagnosis & Development, Indiana University School of Medicine, Suite 314, 320 West 15th Street, Indianapolis, IN, 46202, USA. robchamb@iupui.edu.; Addiction Psychiatry Training Program, IU Neuroscience Research Center, Indiana University School of Medicine, Suite 314, 320 West 15th Street, Indianapolis, IN, 46202, USA. robchamb@iupui.edu.
Jazyk: angličtina
Zdroj: Psychopharmacology [Psychopharmacology (Berl)] 2016 Dec; Vol. 233 (23-24), pp. 3933-3945. Date of Electronic Publication: 2016 Sep 17.
DOI: 10.1007/s00213-016-4421-8
Abstrakt: Rational: Prefrontal cortical (PFC)-hippocampal-striatal circuits, interconnected via glutamatergic signaling, are dysfunctional in mental illnesses that involve addiction vulnerability.
Objectives: In healthy and neurodevelopmentally altered rats, we examined how Radial Arm Maze (RAM) performance estimates addiction vulnerability, and how starting a glutamatergic modulating agent, N-acetyl cysteine (NAC) in adolescence alters adult mental illness and/or addiction phenotypes.
Methods: Rats with neonatal ventral hippocampal lesions (NVHL) vs. SHAM-operated controls were randomized to NAC vs. saline in adolescence followed by cognitive testing (RAM) in early adulthood and then cocaine behavioral sensitization (experiment 1; n = 80) or nicotine self-administration (experiment 2; n = 12).
Results: In experiment 1, NVHL rats showed over-consumption of food (Froot-Loops (FL)) baiting the RAM with poor working memory (low-arm entries to repeat (ETR)), producing an elevated FL to ETR ratio ("FLETR"; p < 0.001). FLETR was the best linear estimator (compared to FL or ETR) of magnitude of long-term cocaine sensitization (R 2  = 0.14, p < 0.001). NAC treatment did not alter FL, ETR, FLETR, or cocaine sensitization. In experiment 2, FLETR also significantly and uniquely correlated with subsequent drug seeking during nicotine-induced reinstatement after extinction of nicotine self-administration (R 2  = 0.47, p < 0.01). NAC did not alter RAM performance, but significantly reversed NVHL-induced increases in nicotine seeking during extinction and reinstatement.
Conclusions: These findings demonstrate the utility of animal models of mental illness with addiction vulnerability for developing novel diagnostic measures of PFC-hippocampal-striatal circuit dysfunction that may reflect addiction risk. Such tests may direct pharmacological treatments prior to adulthood and addictive drug exposure, to prevent or treat adult addictions.
Databáze: MEDLINE
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