Adenosine receptors and brain diseases: neuroprotection and neurodegeneration.

Dopamine is an inhibitory neurotransmitter involved in the pathology of schizophrenia. The revised dopamine hypothesis states that dopamine abnormalities in the mesolimbic and prefrontal brain regions exist in schizophrenia. However, recent research has indicated that glutamate, GABA, acetylcholine, and serotonin alterations are also involved in the pathology of schizophrenia. This review provides an in-depth analysis of dopamine in animal models of schizophrenia and also focuses on dopamine and cognition. Furthermore, this review provides not only an overview of dopamine receptors and the antipsychotic effects of treatments targeting them but also an outline of dopamine and its interaction with other neurochemical models of schizophrenia. The roles of dopamine in the evolution of the human brain and human mental abilities, which are affected in schizophrenia patients, are also discussed.

/pdf/the-role-of-dopamine-in-schizophrenia-from-a-neurobiological-131p879297.pdf

The Role of Dopamine in Schizophrenia from a Neurobiological and Evolutionary Perspective: Old Fashioned, but Still in Vogue

http://www.limef.com/downloads/bussey-paper.pdf

New translational assays for preclinical modelling of cognition in schizophrenia: the touchscreen testing method for mice and rats

Cortical information processing is under state-dependent control of subcortical neuromodulatory systems Although this modulatory effect is thought to be mediated mainly by slow nonsynaptic metabotropic receptors, other mechanisms, such as direct synaptic transmission, are possible Yet, it is currently unknown if any such form of subcortical control exists Here, we present direct evidence of a strong, spatiotemporally precise excitatory input from an ascending neuromodulatory center Selective stimulation of serotonergic median raphe neurons produced a rapid activation of hippocampal interneurons At the network level, this subcortical drive was manifested as a pattern of effective disynaptic GABAergic inhibition that spread throughout the circuit This form of subcortical network regulation should be incorporated into current concepts of normal and pathological cortical function

https://science.sciencemag.org/content/sci/326/5951/449.full.pdf

Fast Synaptic Subcortical Control of Hippocampal Circuits

The term neuroplasticity encompasses structural and functional modifications of neuronal connectivity. Abnormal neuroplasticity is involved in various neuropsychiatric diseases, such as dystonia, epilepsy, migraine, Alzheimer's disease, fronto-temporal degeneration, schizophrenia, and post cerebral stroke. Drugs affecting neuroplasticity are increasingly used as therapeutics in these conditions. Neuroplasticity was first discovered and explored in animal experimentation. However, non-invasive brain stimulation (NIBS) has enabled researchers recently to induce and study similar processes in the intact human brain. Plasticity induced by NIBS can be modulated by pharmacological interventions, targeting ion channels, or neurotransmitters. Importantly, abnormalities of plasticity as studied by NIBS are directly related to clinical symptoms in neuropsychiatric diseases. Therefore, a core theme of this review is the hypothesis that NIBS-induced plasticity can explore and potentially predict the therapeutic efficacy of CNS-acting drugs in neuropsychiatric diseases. We will (a) review the basics of neuroplasticity, as explored in animal experimentation, and relate these to our knowledge about neuroplasticity induced in humans by NIBS techniques. We will then (b) discuss pharmacological modulation of plasticity in animals and humans. Finally, we will (c) review abnormalities of plasticity in neuropsychiatric diseases, and discuss how the combination of NIBS with pharmacological intervention may improve our understanding of the pathophysiology of abnormal plasticity in these diseases and their purposeful pharmacological treatment.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.2012.232975

Rodrigo D. Paz

Papers

Glutamatergic dysfunction in schizophrenia: From basic neuroscience to clinical psychopharmacology

Interplay Between Dopamine and Acetylcholine in the Modulation of Attention

Monoamine-Based Treatments in Schizophrenia: Time to Change the Paradigm?