Effects of dopamine transporter changes in the ventral tegmental area of the midbrain on cognitive function in aged rats.

The pathogenesis of Perioperative neurocognitive disorders (PND) is a synergistic effect of many factors. Up to now, the exact mechanism remains unclear. The dopamine pathway in the brain is one of the paths involved in the means of cognitive function. Therefore, the purpose of this study was to investigate the relationship between changes in dopamine transporters in the ventral tegmental area (VTA) of the midbrain and postoperative cognitive dysfunction in elderly rats. In this study, a mental dysfunction model in elderly rats was established after splenectomy under general anesthesia. Eighty male SD rats, aged 18-20 months, with a body mass of 300-500 g. Randomly divided into eight groups: Normal group (Normal, N) and Sham group (sham, S), Model 3 day group(PND, P3), Model 7 day group(PND, P7), Virus 3 days AAV·DAT·RNAi (AAV3), Virus 7 days AAV·DAT·RNAi (AAV7), Virus control for three days AAV·NC(NC3), Virus control for seven days AAV·NC(NC7). The results show that knockdown of dopamine transporter in the VTA region can significantly improve the cognitive dysfunction of elderly rats after surgery. These results suggest that dopamine transporter in the VTA region is involved in cognitive dysfunction in elderly rats. The effect of DAT changes in the VTA region on postoperative cognitive function in elderly rats may be related to the regulation of α-syn and Aß1-42 protein aggregation in the hippocampus.

Protocol of a single group prospective observational study on the diagnostic value of 3T susceptibility weighted MRI of nigrosome-1 in patients with parkinsonian symptoms: the N3iPD study (nigrosomal iron imaging in Parkinson's disease).

INTRODUCTION: Parkinson's disease (PD) is the most common movement disorder in the elderly and is characterised clinically by bradykinesia, tremor and rigidity. Diagnosing Parkinson's can be difficult especially in the early stages. High-resolution nigrosome MRI offers promising diagnostic accuracy of patients with established clinical symptoms; however, it is unclear whether this may help to establish the diagnosis in the early stages of PD, when there is diagnostic uncertainty. In this scenario, a single photon emission CT scan using a radioactive dopamine transporter ligand can help to establish the diagnosis, or clinical follow-up may eventually clarify the diagnosis. A non-invasive, cost-effective diagnostic test that could replace this would be desirable. We therefore aim to prospectively test whether nigrosome MRI is as useful as DaTSCAN to establish the correct diagnosis in people with minor or unclear symptoms suspicious for PD. METHODS AND ANALYSIS: In a prospective study we will recruit 145 patients with unclear symptoms possibly caused by Parkinson's from three movement disorder centres in the UK to take part in the study. We will record the Movement Disorder Society - Unified Parkinson's Disease Rating Scale, and participants will undergo DaTSCAN and high-resolution susceptibility weighted MRI at a field strength of 3T. DaTSCANs will be assessed visually and semiquantitatively; MRI scans will be visually assessed for signal loss in nigrosome-1 by blinded investigators. We will compare how the diagnosis suggested by MRI compares with the diagnosis based on DaTSCAN and will also validate the diagnosis based on the two tests with a clinical examination performed at least 1 year after the initial presentation as a surrogate gold standard diagnostic test. ETHICS AND DISSEMINATION: The local ethics commission (Health Research Authority East Midlands - Derby Research Ethics Committee) has approved this study (REC ref.: 16/EM/0229). The study is being carried out under the principles of the Declaration of Helsinki (64th, 2013) and Good Clinical Practice standards. We have included a number of 15 research-funded DaTSCAN in the research protocol. This is to compensate for study site-specific National Health Service funding for this investigation in affected patients. We therefore have also obtained approval from the Administration of Radioactive Substances Administration Committee (ARSAC Ref 253/3629/35864). All findings will be presented at relevant scientific meetings and published in peer-reviewed journals, on the study website, and disseminated in lay and social media where appropriate. TRIAL REGISTRATION NUMBER: NCT03022357; Pre-results.

Role of the agranular insular cortex in contextual control over cocaine-seeking behavior in rats.

RATIONALE: Environmental stimulus control over drug relapse requires the retrieval of context-response-cocaine associations, maintained in long-term memory through active reconsolidation processes. Identifying the neural substrates of these phenomena is important from a drug addiction treatment perspective. OBJECTIVES: The present study evaluated whether the agranular insular cortex (AI) plays a role in drug context-induced cocaine-seeking behavior and cocaine memory reconsolidation. METHODS: Rats were trained to lever press for cocaine infusions in a distinctive context, followed by extinction training in a different context. Rats in experiment 1 received bilateral microinfusions of vehicle or a GABA agonist cocktail (baclofen and muscimol (BM)) into the AI or the overlying somatosensory cortex (SSJ, anatomical control region) immediately before a test of drug-seeking behavior (i.e., non-reinforced lever presses) in the previously cocaine-paired context. The effects of these manipulations on locomotor activity were also assessed in a novel context. Rats in experiment 2 received vehicle or BM into the AI after a 15-min reexposure to the cocaine-paired context, intended to reactivate context-response-cocaine memories and initiate their reconsolidation. The effects of these manipulations on drug context-induced cocaine-seeking behavior were assessed 72 h later. RESULTS: BM-induced pharmacological inactivation of the AI, but not the SSJ, attenuated drug context-induced reinstatement of cocaine-seeking behavior without altering locomotor activity. Conversely, AI inactivation after memory reactivation failed to impair subsequent drug-seeking behavior and thus cocaine memory reconsolidation. CONCLUSIONS: These findings suggest that the AI is a critical element of the neural circuitry that mediates contextual control over cocaine-seeking behavior.