TY - JOUR
T1 - Effects of sodium butyrate on methamphetamine-sensitized locomotor activity
AU - Harkness, John H.
AU - Hitzemann, Robert J.
AU - Edmunds, Stephanie
AU - Phillips, Tamara J.
N1 - Funding Information:
This work was supported by the Department of Veterans Affairs , and NIDA/NIH grants T32DA07262 and P50DA018165 . Thank you to James Stafford for helpful discussions regarding the IHC procedure and interpretation.
PY - 2013/2/15
Y1 - 2013/2/15
N2 - Neuroadaptations associated with behavioral sensitization induced by repeated exposure to methamphetamine (MA) appear to be involved in compulsive drug pursuit and use. Increased histone acetylation, an epigenetic effect resulting in altered gene expression, may promote sensitized responses to psychostimulants. The role of histone acetylation in the expression and acquisition of MA-induced locomotor sensitization was examined by measuring the effect of histone deacetylase inhibition by sodium butyrate (NaB). For the effect on expression, mice were treated repeatedly with MA (10 days of 2. mg/kg MA) or saline (10 days), and then vehicle or NaB (630. mg/kg, intraperitoneally) was administered 30 min prior to MA challenge and locomotor response was measured. NaB treatment increased the locomotor response to MA in both acutely MA treated and sensitized animals. For acquisition, NaB was administered 30. min prior to each MA exposure (10 days of 1 or 2. mg/kg), but not prior to the MA challenge test. Treatment with NaB during the sensitization acquisition period significantly increased locomotor activation by MA in sensitized mice only. NaB alone did not significantly alter locomotor activity. Acute NaB or MA, but not the combination, increased striatal acetylation at histone H4. Repeated treatment with MA, but not NaB or MA plus NaB, increased striatal acetylation at histone H3. Although increased histone acetylation may alter the expression of genes involved in acute locomotor response to MA and in the acquisition of MA-induced sensitization, results for acetylation at H3 and H4 showed little correspondence with behavior.
AB - Neuroadaptations associated with behavioral sensitization induced by repeated exposure to methamphetamine (MA) appear to be involved in compulsive drug pursuit and use. Increased histone acetylation, an epigenetic effect resulting in altered gene expression, may promote sensitized responses to psychostimulants. The role of histone acetylation in the expression and acquisition of MA-induced locomotor sensitization was examined by measuring the effect of histone deacetylase inhibition by sodium butyrate (NaB). For the effect on expression, mice were treated repeatedly with MA (10 days of 2. mg/kg MA) or saline (10 days), and then vehicle or NaB (630. mg/kg, intraperitoneally) was administered 30 min prior to MA challenge and locomotor response was measured. NaB treatment increased the locomotor response to MA in both acutely MA treated and sensitized animals. For acquisition, NaB was administered 30. min prior to each MA exposure (10 days of 1 or 2. mg/kg), but not prior to the MA challenge test. Treatment with NaB during the sensitization acquisition period significantly increased locomotor activation by MA in sensitized mice only. NaB alone did not significantly alter locomotor activity. Acute NaB or MA, but not the combination, increased striatal acetylation at histone H4. Repeated treatment with MA, but not NaB or MA plus NaB, increased striatal acetylation at histone H3. Although increased histone acetylation may alter the expression of genes involved in acute locomotor response to MA and in the acquisition of MA-induced sensitization, results for acetylation at H3 and H4 showed little correspondence with behavior.
KW - Addiction
KW - Epigenetics
KW - Histone acetylation
KW - Psychostimulant
KW - Sensitization
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U2 - 10.1016/j.bbr.2012.10.046
DO - 10.1016/j.bbr.2012.10.046
M3 - Article
C2 - 23137698
AN - SCOPUS:84870260130
SN - 0166-4328
VL - 239
SP - 139
EP - 147
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 1
ER -