Neuropharmacology
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Unraveling the molecular mechanisms governing long-term synaptic plasticity is a key to understanding how the brain stores information in neural circuits and adapts to a changing environment. Brain-derived neurotrophic factor (BDNF) has emerged as a regulator of stable, late phase long-term potentiation (L-LTP) at excitatory glutamatergic synapses in the adult brain. ⋯ Finally, we explore the inter-relationships between BDNF-regulated mechanisms, how these mechanisms contribute to different forms of L-LTP in the hippocampus and dentate gyrus, and outline outstanding issues for future research. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.
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In recent years, neuroscientists have produced profound conceptual and mechanistic advances on the neurocircuitry of reward and substance use disorders. Here, we will provide a brief review of intracranial drug self-administration and optogenetic self-stimulation studies that identified brain regions and neurotransmitter systems involved in drug- and reward-related behaviors. Also discussed is a theoretical framework that helps to understand the functional properties of the circuitry involved in these behaviors. ⋯ That is, abused drugs or, at least, some may act on basic motivation and mood processes, regulating behavior-environment interaction. Optogenetics and related technologies have begun to uncover detailed circuit mechanisms linking key brain regions in which abused drugs act for rewarding effects. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.
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The adolescent brain is a period of dynamic development making it vulnerable to environmental factors such as drug exposure. Of the illicit drugs, cannabis is most used by teenagers since it is perceived by many to be of little harm. This perception has led to a growing number of states approving its legalization and increased accessibility. ⋯ We provide an overview of the endocannabinoid system in relation to adolescent cannabis exposure and provide insights regarding factors such as genetics and behavioral traits that confer risk for subsequent addiction. While it is clear that more systematic scientific studies are needed to understand the long-term impact of adolescent cannabis exposure on brain and behavior, the current evidence suggests that it has a far-reaching influence on adult addictive behaviors particularly for certain subsets of vulnerable individuals. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.
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Parkinson's disease (PD) is the most common neurodegenerative motor disease. Pathologically, PD is characterized by Lewy body deposition and subsequent death of dopamine neurons in the substantia nigra pars compacta. PD also consistently features degeneration of the locus ceruleus, the main source of norepinephrine in the central nervous system. ⋯ In contrast, the ventral tegmental area, which is spared in human PD, remained unaffected. The coordinate loss of dopamine and norepinephrine neurons in VMAT2 LO mice parallels the pattern of neurodegeneration that occurs in human PD, and demonstrates that insufficient catecholamine storage can cause spontaneous degeneration in susceptible neurons, underscoring cytosolic catecholamine catabolism as a determinant of neuronal susceptibility in PD. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.
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Type 2 diabetes is a risk factor in the development of Alzheimer's disease (AD). It has been shown that insulin signalling is desensitised in the brains of AD patients. The incretin hormone Glucagon-like peptide-1 (GLP-1) facilitates insulin signalling, and long-lasting analogues such as liraglutide (Victoza(®)) are on the market as type 2 diabetes treatments. ⋯ These results demonstrate that Liraglutide not only has preventive properties, but also can reverse some of the key pathological hallmarks of AD. Liraglutide is now being tested in clinical trials in AD patients. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.