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Although the role of epigenetics in Parkinson's disease (PD) has not been extensively studied, α-synuclein, the main component of Lewy bodies, decreased histone H3 acetylation. Here, we determined if there were histone acetylation changes in the primary motor cortex which, according to the Braak model, is one of the last brain regions affected in PD. Net histone H3 acetylation, histone H3 lysine 9 (H3K9), histone H3 lysine 14 (H3K14), histone H3 lysine 18 (H3K18), and histone H3 lysine 23 (H3K23) acetylation was assessed in the primary motor cortex of those affected and unaffected by PD. There was net increase in histone H3 acetylation due to increased H3K14 and H3K18 acetylation. There was a decrease in H3K9 acetylation. No between-groups difference was detected in H3K23 acetylation. Relationships between Unified Lewy Body Staging scores and histone H3 acetylation and substantia nigra depigmentation scores and histone H3 acetylation were observed. No relationships were detected between postmortem interval and histone H3 acetylation and expired age and histone H3 acetylation. These correlational data support the notion that the histone H3 acetylation changes observed here are not due to the postmortem interval or aging. Instead, they are due to PD and/or factors that covary with PD. The data suggest enhanced gene transcription in the primary motor cortex of the PD brain due to increase H3K14 and H3K18 acetylation. This effect is partially offset by a decreased H3K9 acetylation, which might repress gene transcription.

The lead (Pb) chelator, meso-2,3-dimercaptosuccinic acid (DMSA) may be effective in reversing some of the adverse effects of Pb exposure. Pb-induced behavioral deficits observed in fish are due to disruptions in the integrative functioning of the medulla, cerebellum, and optic tectum. Pb exposure increased serotonin (5-HT) content in all three brain regions without an effect on 5-hydroxy-3-indoleacetic acid (5-HIAA). Pb exposure followed by no Pb in the diet increased 5-HT and 5-HIAA content in all three brain regions. The replacement of dietary Pb with DMSA had no effect on 5-HT and increased 5-HIAA content. DMSA increased 5-HIAA content in all three brain regions and increased 5-HT content only the optic tectum. Treatment with DMSA may be more effective than removal of Pb from the diet in reversing Pb-induced alterations in 5-HT.

Administration of the non-selective opioid receptor antagonists, naloxone and naltrexone, attenuate the rewarding effects of cocaine. The relative contributions of specific opioid receptor subtypes that underlie this effect have not been well characterized. Administration of 20.0 mg/kg cocaine resulted in a conditioned place preference. Pretreatment with 20.0 mg/kg but neither 10.0 nor 1.0 mg/kg of the selective mu(1)-opioid receptor antagonist, naloxonazine, blocked cocaine-induced conditioned place preference. On the days in which rats received cocaine only, locomotor behavior was elevated. Pretreatment with the selective mu(1)-opioid receptor antagonist, naloxonazine, regardless of dose, had no effect on cocaine-induced hyperlocomotion. These findings indicate that the rewarding effects of cocaine can be blocked solely by mu(1)-opioid receptor antagonism and are consistent with the view that the locomotor and rewarding effects of drugs can be dissociated.