In addition, the pathophysiology of TD remains elusive and therapeutics are difficult. Based on rodent experiments, we have previously shown that the transcriptional factor Nur77 (also known as nerve growth factor inducible gene B or Nr4a1) is induced in the striatum following antipsychotic drug exposure as part of a long-term neuroadaptive process. To confirm this, Inhibitor Library high throughput we exposed adult capuchin (Cebus apella) monkeys to prolonged treatments with haloperidol (median 18.5 months, N = 11) or clozapine (median 6 months, N = 6). Six untreated animals were used as controls. Five haloperidol-treated animals developed mild TD movements similar to those found

in humans. No TD was observed in the clozapine group. SP600125 order Postmortem analysis of Nur77 expression measured by in situ hybridization revealed a stark contrast between the two drugs, as Nur77 mRNA levels in the caudate-putamen were strongly upregulated in animals exposed to haloperidol but were spared following clozapine treatment. Interestingly, within the haloperidol-treated group, TD-free animals showed higher Nur77 expression in putamen subterritories compared with dyskinetic animals. This suggests that Nur77 expression might be associated with a reduced risk of TD in this experimental model and could provide a novel target for drug

intervention. “
“Ligustilide (LIG) is a major component of Radix Angelica Sinensis, and reportedly has neuroprotective and anti-inflammatory effects. Recent studies have demonstrated that spinal astrocyte-mediated neuroinflammation plays an important role in the pathogenesis

of chronic pain. Here we investigated the anti-nociceptive effect of systemic treatment with LIG on chronic inflammatory pain and explored possible mechanisms. Unilateral hindpaw injection of complete Freund’s adjuvant (CFA) induced persistent pain hypersensitivity. Repeated daily intravenous treatment with LIG, either before or after CFA injection, attenuated CFA-induced thermal hyperalgesia and mechanical allodynia. The same treatment also inhibited CFA-induced keratinocyte-derived chemokine (KC) and monocyte chemoattractant protein-1 (MCP-1) mRNA and protein increases in astrocytes of the spinal cord. In vitro study showed LIG dose-dependently reduced lipopolysaccharide (LPS)-induced upregulation of KC and MCP-1 mRNA in astrocyte cultures. Ibrutinib molecular weight Interestingly, LIG treatment did not affect CFA- or LPS-induced glial fibrillary acidic protein upregulation, but did inhibit CFA-induced phosphorylated nuclear factor-κB (p-NFκB) upregulation in spinal astrocytes. Furthermore, intrathecal injection of NFκB inhibitor attenuated CFA-induced pain hypersensitivity and upregulation of KC and MCP-1 in the spinal cord. Finally, single intravenous injection of LIG attenuated intrathecal injection of LPS-induced mechanical allodynia. The same treatment also decreased LPS-induced NFκB activation and KC and MCP-1 upregulation in the spinal cord.