Contrary to the inhibition account but consistent with selective rehearsal, we found for both remember and forget items that recognition was greater in the mixed than in the pure condition. Recognition for forget items also did not differ from neutral items. We conclude that selective rehearsal, not inhibition, is responsible for item-method directed forgetting.Deep brain stimulation (DBS) of reward system brain areas, such as the medial forebrain bundle (MFB), by means of intracranial self-stimulation (ICSS), facilitates learning and memory in rodents. MFB-ICSS has been found capable of modifying different plasticity-related proteins, but its underlying molecular mechanisms require further elucidation. MicroRNAs (miRNAs) and the longevity-associated SIRT1 protein have emerged as important regulatory molecules implicated in neural plasticity. Thus, we aimed to analyze the effects of MFB-ICSS on miRNAs expression and SIRT1 protein levels in hippocampal subfields and serum. We used OpenArray to select miRNA candidates differentially expressed in the dentate gyrus (DG) of ICSS-treated (3 sessions, 45' session/day) and sham rats. We further analyzed the expression of these miRNAs, together with candidates selected after bibliographic screening (miR-132-3p, miR-134-5p, miR-146a-5p, miR-181c-5p) in DG, CA1, and CA3, as well as in serum, by qRT-PCR. We also assessed tissue and serum SIRT1 protein levels by Western Blot and ELISA, respectively. Expression of miR-132-3p, miR-181c-5p, miR-495-3p, and SIRT1 protein was upregulated in DG of ICSS rats (P  less then  0.05). None of the analyzed molecules was regulated in CA3, while miR-132-3p was also increased in CA1 (P = 0.011) and serum (P = 0.048). OD36 RIP kinase inhibitor This work shows for the first time that a DBS procedure, specifically MFB-ICSS, modulates the levels of plasticity-related miRNAs and SIRT1 in specific hippocampal subfields. The mechanistic role of these molecules could be key to the improvement of memory by MFB-ICSS. Moreover, regarding the proposed clinical applicability of DBS, serum miR-132 is suggested as a potential treatment biomarker.BACKGROUND AND OBJECTIVES Driving under the influence of diazepam is increasing in China. The pharmacokinetics of diazepam and its metabolites, especially the glucuronide metabolites, are helpful in the identification of diazepam use by drivers. This study aimed to investigate the pharmacokinetics of diazepam and its metabolites (nordazepam, oxazepam, oxazepam glucuronide and temazepam glucuronide) in the blood of Chinese people, and to provide basic data for identifying diazepam use and estimating the time of last diazepam ingestion. METHODS A total of 28 participants (14 men, 14 women) were recruited and each person received 5 mg diazepam orally. Whole blood was collected at 0 h (pre-dose), and 1 h, 2 h, 4 h, 8 h, 12 h, and 24 h, and at 2 days, 3 days, 6 days, 12 days, and 15 days post-dose. Analytes of interest were extracted via solid-phase extraction and analyzed by a liquid chromatography tandem mass spectrometry method operated in a positive multiple response monitoring mode. Pharmacokinetic parametersepam ingestion by monitoring diazepam and its metabolites including glucuronides, as well as to infer the time following oral consumption.The relationship between the 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) and depression in Parkinson's disease (PD) has remained controversial. Therefore, we conducted this meta-analysis to evaluate the relationship between 5-HTTLPR polymorphisms and depression in PD. Relevant online databases were searched for cross-sectional, case-control or cohort studies examining relations between 5-HTTLPR polymorphisms (S/L) and the risk of developing depression of PD using a meta-analysis. Odd ratios (ORs) of 5-HTTLPR polymorphisms (S/L allele genotype) were calculated between depression in PD and PD for each study. Five observational studies were identified. Overall ORs for 5-HTTLPR S-Allele genotype was 1.98 (95% CI 0.92-4.26) in the dominant model, 1.43 (95% CI 1.08-1.90) in the recessive model, 2.64 (95% CI 1.01-6.88) in the additive model, independently. The overall ORs of S-Allele genotype was 1.51 (95% CI 0.63-3.64) for the Caucasian subgroup, and 1.44 (95% CI 1.05-1.98) for the non-Caucasian subgroup in the recessive model. This meta-analysis indicates that the 5-HTTLPR genotype (S/S-Allele) is correlated with an increased depression risk in PD, and this highlights the needs for these people to take some effective approaches (if any) in prevention of depression of PD before its onset.BACKGROUND Disturbances of dopaminergic and glutamatergic transmissions have been suggested to be involved in the pathomechanisms underlying psychotic symptoms of schizophrenia. In line with this concept, hyperlocomotion induced by the dopaminomimetic amphetamine and the uncompetitive antagonist of NMDA receptors MK-801 (dizocilpine) in rodents is a generally established model for screening of new potential antipsychotic drugs. Since recent studies have indicated that receptors for adenosine may be targets for antipsychotic therapy, the aim of the present study was to investigate an influence of 5'-Cl-5'-deoxy-ENBA, a potent and selective adenosine A1 receptor agonist, on hyperlocomotion induced by amphetamine and MK-801. METHODS Locomotor activity was measured by Force Plate Actimeters where four force transducers located below the corners of the floor of the cage tracked the animal position on a Cartesian plane at each time point. RESULTS Hyperlocomotion induced by either amphetamine (1 mg/kg sc) or MK-801 (0.3 mg/kg ip) was inhibited by 5'-Cl-5'-deoxy-ENBA (0.1 mg/kg ip). The effect of 5'-Cl-5'-deoxy-ENBA on the amphetamine- and MK-801-induced hyperlocomotion was antagonized by the selective antagonist of adenosine A1 receptor DPCPX at doses of 1 and 2 mg/kg ip, respectively. CONCLUSION The present study suggests that stimulation of adenosine A1 receptors may produce antipsychotic effects.BACKGROUND Inhibition of cytochrome P450 (CYP) enzymes is the most common cause of harmful drug-drug interactions. The present study aimed at examining the inhibitory effect of the novel antipsychotic drug asenapine on the main CYP enzymes in human liver. METHODS The experiments were performed in vitro using pooled human liver microsomes and the human cDNA-expressed CYP enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 (Supersomes). Activities of CYP enzymes were determined using the CYP-specific reactions caffeine 3-N-demethylation (CYP1A2), diclofenac 4'-hydroxylation (CYP2C9), perazine N-demethylation (CYP2C19), bufuralol 1'-hydroxylation (CYP2D6), and testosterone 6β-hydroxylation (CYP3A4). The rates of the CYP-specific reactions were assessed in the absence and presence of asenapine using HPLC. RESULTS The obtained results showed that both in human liver microsomes and Supersomes asenapine potently and to a similar degree inhibited the activity of CYP1A2 via a mixed mechanism (Ki = 3.2 μM in liver microsomes and Supersomes) and CYP2D6 via a competitive mechanism (Ki = 1.