No abstract

Glutamate receptors in mesolimbic areas such as the nucleus accumbens, ventral tegmental area, prefrontal cortex (PFC), and hippocampus (HIP) are a component of the mechanisms of drug-induced reward and can modulate the firing pattern of dopaminergic neurons in the reward system. In addition, several lines of study have indicated that cAMP response element-binding protein (CREB) and c-fos have important role in morphine-induced conditioned place preference (CPP) induced by drugs of abuse, such as morphine, cocaine, nicotine, and alcohol. Therefore, in the present study, we investigated the changes in phosphorylated CREB (p-CREB) and c-fos induction within the nucleus accumbens (NAc), HIP, and PFC after intracerebroventricular (ICV) administration of different doses of CNQX or vehicle during extinction period or reinstatement of morphine-induced CPP. In all groups, the CPP procedure was done; afterward, the conditioning scores were recorded by Ethovision software. After behavioral test recording, we dissected out the NAc, HIP, and PFC regions and measured the p-CREB/CREB ratio and c-fos level by Western blot analysis. Our results showed that administration of CNQX significantly shortened the extinction of morphine CPP. Besides, ICV microinjection of CNQX following extinction period decreased the reinstatement of morphine CPP in extinguished rats. In molecular section, in treatment group, all mentioned factors were dose-dependently decreased in comparison with vehicle group (DMSO) after ICV microinjection of different doses of CNQX but not in pre-extinction microinjection. These findings suggested that antagonism of AMPA receptor decreased p-CREB/CREB ratio and c-fos level in the PFC, NAc, and HIP. Modulation of the drug memory reconsolidation may be useful for faster extinction of drug-induced reward and attenuation of drug-seeking behavior.

These findings suggest that hazelnut, as a dietary supplement, improves healthy aging and could be a beneficial diet for the treatment of AD.

Autophagy, the process of self-degradation of cellular components, has an important role in neurodegenerative diseases, such as Alzheimer's disease. In this study, we investigated the effects of SP600125 as c-Jun N-terminal kinase (JNK) inhibitor and bucladesine as a cyclic adenosine 3',5'-monophosphate (cAMP) analog on spatial memory and expression of autophagic factors in Aβ-injected rats. Male Wistar rats were used. Rats were randomly allocated into five groups as following: amyloid beta (Aβ)-only group, Aβ + SP600125 (30 μg/1 μ/side, n = 7) and/or bucladesine (100 μM/1 μl/side, n = 7), and the normal control (vehicle only) group. The treatments were administered bilaterally to the CA1 sub-region of the hippocampus stereotaxically. Spatial reference memory was performed using Morris Water Maze 21 days later. The expression of authophagy markers (beclin1, Atg7, Atg12, and LC3 II/LC3 I) in the hippocampus was evaluated using western blotting. Compared to the vehicle group, Aβ administration reduced spatial reference learning (P < 0.001) and memory (P < 0.01) and upregulated the expression of beclin1, Atg7, Atg12, and LC3 II/I (P < 0.0001). Compare to Aβ-only group, the administration of SP600125 and/or bucladesine improved spatial reference learning (P < 0.001) and memory (P < 0.01). Compared to the Aβ-only group, the treatment with SP600125 and/or bucladesine also reduced beclin1, Atg7, Atg12, and LC3 II/I (P < 0.0001) which was similar to amount of normal rats. In summary, it seems that the improvement of spatial memory by SP600125 and/or bucladesine in Aβ-injected rats is in relation with normalizing of autophagy to the physiologic level, possibly through neuroprotection and/or neuroplasticity.

Allium hirtifolium Boiss and Astragalus hamosus L. are mentioned in Iranian traditional medicine documentation as therapy for a kind of dementia with the features and symptoms similar to those of Alzheimer's disease (AD). In the present study, the effects of these herbs on neuro-inflammation and memory have been evaluated as new therapies in amyloid beta (Aβ)-induced memory impairment model. Separate groups of rats were fed with A. hirtifolium or A. hamosus extract (both 100 mg/(kg·day)) started 1 week before stereotaxic surgery to 24 h before behavioral testing (totally, for 16 successive days). The effects of oral administration of mentioned extracts on the memory and neuro-inflammation were assessed in the Aβ-injected rats. The results of this study showed that oral administration of both A. hirtifolium and A. hamosus improved the memory, examined by using Y-maze test and shuttle box apparatus. Also, Western blotting analysis of cyclooxygenase-2, interleukin-1β, and tumor necrosis factor-α showed that these herbs have ameliorating effects against the neuro-inflammation caused by Aβ. These findings suggest that the use of A. hirtifolium and A. hamosus as herbal therapy may be suitable for decreasing AD-related symptoms and treatment of other neurodegenerative disorders.