Persistent changes in behavior and psychological function that occur as a consequence of exposure to drugs of abuse are thought to be mediated by the structural plasticity of specific neural circuits such as the brain’s dopamine (DA) system. Changes in dendritic morphology in the nucleus accumbens (NAc) accompany druginduced enduring behavioral and molecular changes, yet ultrastructural changes in synapses following repeated exposure to drugs have not been well studied. The current study examines the role of DA D3 receptors in modulating locomotor activity induced by both acute and repeated methamphetamine (METH) administration and accompanying ultrastructural plasticity in the shell of NAc in mice. We found that D3 receptor mutant (D3−/−) mice exhibited attenuated acute locomotor responses as well as the development of behavioral sensitization to METH compared with wild-type mice. In the absence of obvious neurotoxic effects, METH induced similar increases in synaptic density in the shell of NAc in both wild-type and D3−/− mice. These results suggest that D3 receptors modulate locomotor responses to both acute and repeated METH treatment. In contrast, the D3 receptor is not obviously involved in modulating baseline or METH-induced ultrastructural changes in the NAc shell.

Drugs of abuse modulated learning and memory in humans yet the underlying mechanism remained unclear. The extracellular signal-regulated kinase (ERK) and the transcription factor cAMP response element-binding protein (CREB) were involved in neuroplastic changes associated with learning and memory. In the current study, we used a Morris water maze to examine the effect of methamphetamine (METH) on different processes of spatial memory in mice. We then investigated the status of ERK and CREB in the hippocampus and prefrontal cortex (PFC). We found that 1.0 mg/kg dose of METH facilitated spatial memory consolidation when it was injected immediately after the last learning trial. In contrast, the same dose of METH had no effect on spatial memory retrieval when it was injected 30 min before the test. Furthermore, 1.0 mg/kg dose of METH injected immediately after retrieval had no effect on spatial memory reconsolidation. Activation of both ERK and CREB in the hippocampus was found following memory consolidation but not after retrieval or reconsolidation in METH-treated mouse groups. In contrast, activation of both ERK and CREB in the PFC was found following memory retrieval but not other processes in METH-treated mouse groups. These results suggested that METH facilitated spatial memory consolidation but not retrieval or reconsolidation. Moreover, activation of the ERK and CREB signaling pathway in the hippocampus might be involved in METH-induced spatial memory changes.

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This study aimed to investigate the effects of curcumin on macrophages polarization and possible mechanism involved, and to analyze the molecular basis of its antiatherosclerosis activity. RAW264.7 macrophages (M0) and M1 macrophages were treated with curcumin at 0, 6.25, 12.5, and 25 μmol/L with or without GW9662. Using real-time polymerase chain reaction and Western blot analysis, we examined the phenotype markers of M1 [iNOS, interleukin (IL)-1β, IL-6, and MCP-1] and M2 (KLF4, FIZZ1, and MGL1] macrophages. Curcumin reduced the expression of the M1 phenotype markers and upregulated the expression of proliferator-activated receptor γ in M0 and M1 macrophages and IKBα in M1 macrophages. When M1 macrophages were incubated with curcumin and GW9662, the expression of the M1 phenotype markers was decreased, while IKBα was upregulated. The expression of the M2 phenotype markers in M0 and M1 macrophages was upregulated after the curcumin treatment. When M0 and M1 macrophages were incubated with curcumin and GW9662, the expression of the M2 phenotype markers was reduced. Curcumin inhibited the M1 inflammation phenotype as a result of the direct activation of IKBα and polarized the macrophages to become M2 phenotype through the activation of proliferator-activated receptor γ. These findings provide new clues to develop new drug therapy for atherosclerosis.

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