Effects of sodium butyrate on methamphetamine-sensitized locomotor activity

Abstract

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, vehicle or NaB (630 mg/kg, intraperitoneally) was administered 30 min prior to MA challenge in mice treated repeatedly with MA (10 days of 2 mg/kg MA) or saline (10 days), and then locomotor response to MA challenge 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, appeared to increase 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.

Epigenetics and addiction

“…Moreover, METH upregulated Egr2 and c‐fos expression via increased H4K5Ac binding at the promoters of these genes . In a subsequent article, Harkness et al . also reported that acute METH increased H4 acetylation in the striatum.…”

“…Moreover, METH upregulated Egr2 and c-fos expression via increased H4K5Ac binding at the promoters of these genes. 62 In a subsequent article, Harkness et al 63 also reported that acute METH increased H4 acetylation in the striatum. It is thus possible that METH-induced increased H4 acetylation may be secondary to increased CBP expression because increased CBP expression is associated with increased histone acetylation.…”

Methamphetamine Induces Dynamic Changes of Histone Deacetylases in Different Phases of Behavioral Sensitization

“…Knockout of HDAC5 promoted the hypersensitive responses, which was completely reversed by re-expression of HDAC5 in NAc [7]. Our present study further suggested the special role of HDAC5 in METH-induced behavioral sensitization.Administration of HDAC inhibitors (HDACis) increased histone acetylation in the central nervous system and was supposed to modulate drug addiction [8,9]. However, different HDACis were reported to have different, even opposite effects on drug addiction.…”

“…Administration of HDAC inhibitors (HDACis) increased histone acetylation in the central nervous system and was supposed to modulate drug addiction [8,9]. However, different HDACis were reported to have different, even opposite effects on drug addiction.…”

“…However, different HDACis were reported to have different, even opposite effects on drug addiction. Valproic acid (VPA), the Class I and Class II HDACi, inhibited the development of behavioral sensitization induced by METH [8]; however, sodium butyrate (SB), another kind of Class I and Class II HDACi, led to the enhancement of behavioral sensitization [9]. The mechanism for the different effects of HDACis has not been well understood, but one study suggested that drug addiction may induce the expression of different transcription factors, which was modified by different HDACis [10].…”