Sodium butyrate-induced histone acetylation strengthens the expression of cocaine-associated contextual memory

• Published in: Neurobiology of learning and memory Vol. 102; pp. 34 - 42
• Main Authors: Itzhak, Yossef, Liddie, Shervin, Anderson, Karen L.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.05.2013; Elsevier; Elsevier BV
• Subjects: Acetylation - drug effects; Amygdala - drug effects; Amygdala - metabolism; Animals; Association Learning - drug effects; Behavioral psychophysiology; Biological and medical sciences; Butyric Acid - pharmacology; Cocaine; Cocaine - administration & dosage; Cocaine - pharmacology; Conditioned place preference; Conditioning, Operant - drug effects; Dopamine Uptake Inhibitors - administration & dosage; Dopamine Uptake Inhibitors - pharmacology; Drug Administration Schedule; Extinction, Psychological - drug effects; Fear - drug effects; Fundamental and applied biological sciences. Psychology; Hippocampus - drug effects; Hippocampus - metabolism; Histone acetylation; Histones - metabolism; Male; Memory - drug effects; Mice; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Sodium butyrate; Sodium butyrate; Histone acetylation; Cocaine; Conditioned place preference; Context; Ester; Sodium; Drug of abuse; Acetylation; Histone
• ISSN: 1074-7427; 1095-9564; 1095-9564
• DOI: 10.1016/j.nlm.2013.03.007

•Na-Butyrate (NaB) increased histone acetylation in mouse hippocampus but not amygdala.•Acute NaB injection prior to cocaine-induced place learning suppressed extinction.•Acute NaB suppressed extinction also when given during place preference testing.•Repeated NaB administration increased cocaine place preference.•The HDAC inhibitor persistently strengthened cocaine-associated contextual memory. The conditioned place preference (CPP) paradigm entails Pavlovian conditioning and allows evaluating the acquisition and extinction of drug-associated memory. Epigenetic regulation of chromatin structure by acetylation and deacetylation of histone proteins is critical for formation of long-term memory (LTM). We have recently shown that a single administration of the histone deacetylase (HDAC) inhibitor sodium butyrate (NaB) facilitated extinction of fear-associated memory in mice. Using the CPP paradigm, the present study investigated the effect of NaB on cocaine-associated memory. C57B/6 mice were conditioned by either fixed daily doses of cocaine (5mg/kg×4 and 15mg/kg×4days) or an escalating schedule (3, 6, 12 and 24mg/kg). Acute administration of NaB (1.2g/kg) prior to conditioning by fixed doses of cocaine increased the expression and impaired the extinction of place preference compared to control subjects. Subjects that were conditioned by 15mg/kg×4 cocaine and received a single injection of NaB following the first or the second CPP test showed impaired extinction compared to control mice that received saline instead of NaB. Subjects that were conditioned by escalating schedule of cocaine and subsequently received repeated injections of NaB during daily reexposure to nonreinforced context showed either enhancement or no effect on place preference. Acute administration of NaB (1.2g/kg) to naïve mice resulted in marked increase in acetylation of histone H3 lysine 14 (H3K14) and histone H4 lysine 8 (H4K8) in hippocampus but not amygdala. Results suggest that regardless of the scheduling of either cocaine or NaB administration, NaB-induced histone hyperacetylation in the hippocampus may strengthen cocaine-associated contextual memory.