Neuroscience
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Research involving animal models of drug addiction can be viewed as a sort of reverse psychiatry. Contrary to clinicians who seek to treat addicted people to become and remain abstinent, researchers seek to make drug-naïve animals addicted to a drug with known addictive properties in humans. The goals of this research are to better understand the neuroscience of drug addiction and, ultimately, to translate this knowledge into effective treatments for people with addiction. ⋯ In fact, it appears that resilience to cocaine addiction is the norm in rats. As in human cocaine users, only few individual rats would be vulnerable. This conclusion has several important implications for future research on the neuroscience of cocaine addiction and on preclinical medication development.
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The prefrontal cortex (PFC) mediates higher-order cognitive and executive functions that subserve various complex, adaptable behaviors, such as cognitive flexibility, attention, and working memory. Deficits in these functions typify multiple neuropsychiatric disorders that are caused or exacerbated by exposure to psychological stress. Here we review recent evidence examining the effects of stress on executive and cognitive functions in rodents and discuss an emerging body of evidence that implicates the N-methyl-D-aspartate receptor (NMDAR) as a potentially critical molecular mechanism mediating these effects. Future work in this area could open up new avenues for developing pharmacotherapies for ameliorating cognitive dysfunction in neuropsychiatric disease.
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Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disorder clinically characterized by a variable combination of dysautonomia, levodopa-unresponsive parkinsonian and cerebellar symptoms. Neurodegeneration in MSA occurs in the substantia nigra, putamen, inferior olive, pontine and brainstem nuclei, as well as intermediolateral cell column of the spinal cord. MSA is recognized as a synucleinopathy due to the accumulation of insoluble alpha-synuclein in oligodendroglial cytoplasmic inclusions. ⋯ Both approaches have then been merged to create optimized, dual-hit models. This review describes the different animal models of MSA, their respective advantages and limitations and their usefulness to decipher the pathophysiology of MSA then to define efficient symptomatic and disease-modifying therapies. This article is part of a Special Issue entitled: Neuroscience Disease Models.
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During the last 30 years there have been many attempts to develop animal models of obsessive compulsive disorder (OCD), in the hope that they may provide a route for furthering our understanding and treatment of this disorder. The present review provides the reader with an overview of the currently active animal models of OCD, their strengths and limitations, so that the reader can use the review as a guide for establishing new animal models of OCD, evaluating existing animal models and choosing among them according to one's needs. ⋯ On the basis of this evaluation we discuss the usefulness of the different models for screening drugs for anti-compulsive activity, detecting new targets for high frequency stimulation, studying the neural mechanisms of OCD and unraveling the role of gonadal hormones. We then describe potential new treatment strategies that emerge from the convergence of data obtained in different models on the one hand, and how different models can be used to model different subtypes or dimensions of OCD, on the other hand.
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In the recent past, the pathogenesis of Parkinson's disease (PD) has evolved from a neurodegenerative disorder considered entirely sporadic to a disease with an unequivocal genetic component. Indeed, different inherited forms of PD have been discovered and characterized, although the functional roles of the gene products identified are still under intense investigation. ⋯ Although most of the rodent models display neither obvious behavioral impairment nor evidence for neurodegeneration, remarkable abnormalities of dopamine-mediated neurotransmission and corticostriatal synaptic plasticity have been described, indicative of a fundamental distortion of network function within the basal ganglia. The picture emerging from a critical review of recent data on monogenic parkinsonisms suggests that mutations in PD genes might cause developmental rearrangements in the corticobasal ganglia circuitry, compensating the dopaminergic dysfunction observed both in mice and humans, in order to maintain proper motor function.