Nucleus Accumbens and Dopamine-Mediated Turning Behavior of the Rat: Role of Accumbal Non-Dopaminergic Receptors.

Nucleus Accumbens and Dopamine-Mediated Turning Behavior of the Rat: Role of Accumbal Non-dopaminergic Receptors.

Filed under: Depression Treatment

J Pharmacol Sci. 2012 Oct 10;
Ikeda H, Kamei J, Koshikawa N, Cools AR

Accumbal dopamine plays an important role in physiological responses and diseases such as schizophrenia, Parkinson’s disease, and depression. Since the nucleus accumbens contains different neurotransmitters, it is important to know how they interact with dopaminergic function: this is because modifying accumbal dopamine has far-reaching consequences for the treatment of diseases in which accumbal dopamine is involved. This review provides a summary of these interactions, and our current knowledge about them are as follows: A) AMPA receptors are required for dopamine-dependent behavior and vice versa; NMDA receptors modulate the activity at the level of AMPA and/or dopamine D(1) receptors. B) GABA(A), but not GABA(B), receptors inhibit dopamine-dependent behavior. C) Nicotinic receptors are required for dopamine-dependent behavior, whereas muscarinic receptors inhibit dopamine-dependent behavior. D) ?-Adrenoceptors inhibit dopamine-dependent behavior in contrast to ?-adrenoceptors, which potentiate this behavior. E) ?- and ?(2)-opioid receptors elicit behavior that requires an intact dopaminergic function and ?(2)-opioid receptors modulate dopamine-dependent behavior. F) Orexin 2 receptors play an important, modifying role in dopamine-dependent behavior. G) Somatostatin receptors potentiate dopamine-dependent behavior. It is suggested that modulation of the above-mentioned non-dopaminergic receptors provide new tools to control physiological functions as well as diseases mediated by accumbal dopamine.
HubMed – depression

The natural history of early-onset dementia: the Artemis Project.

Filed under: Depression Treatment

BMJ Open. 2012; 2(5):
Atkins ER, Bulsara MK, Panegyres PK

The natural history of early-onset Alzheimer’s disease (AD) and fronto-temporal dementia (FTD) remains to be described in detail. We seek to describe the natural history of early onset AD and FTD in terms of changes in cognitive assessment and staging, medical history and survival.Longitudinal prospective cohort analysis.Neurodegenerative disorders research clinic.In total, 155 consecutive patients with clinically confirmed sporadic early-onset AD or FTD at a neurodegenerative disorders research clinic in Subiaco, Western Australia (The Artemis Project).A detailed history was recorded from the patients at baseline, including education, family history and medical history. Mini-mental state exam (MMSE), Global Deterioration Scale (GDS) and total functional capacity (TFC) were determined at each visit from 1994 until 2011. Kaplan-Meier survival analysis was performed.Patients with FTD were more likely to have a family history of dementia (p=0.026), to develop at least one cerebrovascular risk factor (p=0.003), manifest depression (Fisher’s exact p=0.007) and to die during the follow-up period (Pearson ?(2) 8.97, p=0.003). Kaplan-Meier survival estimates revealed a highly significant difference in the proportion of patients surviving the follow-up period (log rank 7.25, p=0.007) with FTD patients experiencing poorer survival than those with AD. The mean MMSE and TFC were consistently lower in those with FTD compared with those with AD over a decade of follow-up; mean GDS was consistently higher in those with FTD over the follow-up period.We believe that the difference in survival in patients with AD and FTD in our cohort might relate to the development of one or more cerebrovascular risk factors in FTD patients and the severity of the underlying pathology.
HubMed – depression

[Managing psychiatric side effects of antiviral therapy in chronic hepatitis C].

Filed under: Depression Treatment

Z Gastroenterol. 2012 Oct; 50(10): 1108-13
Schäfer A, Scheurlen M, Kraus MR

The efficacy of antiviral therapy in patients with chronic hepatitis C virus (HCV) infection has largely improved over the last years. Rates of long-term therapy success (sustained virological response, SVR) clearly exceed 50 % in the population of all antivirally treated HCV patients, even when including the less favourable virus genotypes 1 and 4. From recent research, it is well-known that adherence to current standard combination therapy (peginterferon alfa plus ribavirin) is crucial for the achievement of sustained response. Psychiatric adverse events, however, are subjectively very burdening and are among the most frequent reasons for premature discontinuation of antiviral therapy in HCV patients and therefore endanger therapy success. Therefore, effective side effect management regarding this branch of symptoms (e. g. depression, anger-hostility, anxiety) is to be considered crucial for the achievement of SVR. This review presents a current overview of the most relevant IFN-associated psychiatric side effects in antivirally treated patients with chronic hepatitis C infection. Moreover, various strategies for the management of these undesired conditions are reported: In particular, we address the issues of diagnostics and pretherapeutic screening for risk factors for the subsequent development of IFN-associated psychiatric symptoms. Moreover, we provide an overview of suitable instruments for the psychiatric monitoring of patients on antiviral therapy. We further discuss appropriate treatment strategies (e. g. prophylactic medication vs. medication only after the occurrence of symptoms) as well as indications for immediate therapy discontinuation due to serious psychiatric adverse events. In many cases, premature therapy discontinuation can be prevented by individual and adequate side effect management, provided that it is started in a timely manner. The continuing clinical relevance of psychiatric side effect management in this context is further backed up by the fact that also novel treatment strategies comprising protease or polymerase inhibitors will still include pegylated interferon alfa and ribavirin.
HubMed – depression

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