Historical review: Molecular and cellular mechanisms of opiate and cocaine addiction.
The initial protein targets for almost all drugs of abuse are now known. Animal models that replicate key features of addiction are available, and these models have made it possible to characterize the brain regions that are important for addiction and other drug effects, such as physical dependence. View on PubMed. Alternate Sources. Save to Library. Create Alert.
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Citations Publications citing this paper. Explores how the chemical make-up of drugs interact with the brain and can lead to addiction Includes coverage of a wide array of commonly abused families of drugs, including stimulants, depressants, hallucinogens, and others. Provides an essential introduction to the chemical and molecular underpinnings of drug use and abuse. Amphetamine andAmphetamine Analogs. Morphine and Morphine Analogs.
Lysergic Acid Diethylamide and Mescaline. Benzodiazepines and Barbiturates. We have shown, for example, that dopamine-deficient mice do not manifest a normal locomotor response to amphetamine, but responsiveness can be restored by viral transduction of the nucleus accumbens.
At a more fundamental level, dopamine release in response to rewards e. As a first step, we are asking whether dopamine-deficient mice show a preference for natural or artificial sweets over water, and if so, is dopamine required for associative learning.
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While less attention is directed towards norepinephrine in studies on drug abuse, there are numerous indications that it may also be involved. For example, blockade of a1-adrenoreceptors with prazosin inhibits amphetamine-induced locomotion, suggesting that norepinephrine signaling through these receptors is required for dopamine that is released by amphetamine to elicit locomotion.
We have initiated studies in this area by asking whether chronic norepinephrine deficiency prevents amphetamine-induced locomotion as would be predicted from the observations described above. We discovered, quite unexpectedly, that norepinephrine-deficient mice show an enhanced locomotor response to amphetamine compared to controls. The locomotor response to amphetamine increases with successive administrations of this drug, a phenomenon referred to as sensitization.
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Our norepinephrine-deficient mice behave as though they are already sensitized. Another situation where norepinephrine has been implicated involves withdrawal from chronic morphine treatment. The unpleasant behavioral syndrome that is precipitated during withdrawal has been ascribed to norepinephrine release from the locus coeruleus.
Drugs of Abuse
If this hypothesis is correct, we predict that the behavioral response to withdrawal would be attenuated in mice lacking norepinephrine. Studies exploring this possibility are underway. Nephi Stella, Ph.
My laboratory is interested in how the endogenous cannabinoids anadamide and 2-AG are synthesized and act in the brain. In addition, we are studying the molecular mechanisms involved in the interaction between brain tumors and microglial cells mediated by endocannabinoids. Several in vitro and in vivo experiments using rodent models of astrocytomas have shown that cannabinoid compounds, such as D9-tetrahydrocannabinol THC , inhibit and even reverse tumor growth.
To address the question of whether THC directly kills astrocytomas or modulate immune responses of microglial cells, we are investigating the cannabinoid receptors and their endogenous ligands endocannabinoids , in brain tumors and are testing its role in astrocytomas and microglial cells interaction. Our laboratory uses a variety of models to assess the functionality of the cannabinoid signaling system in brain tumors.
Among these are astrocytes and microglia in primary culture, cultured astrocytomas both primary and transformed cell lines , as well as human biopsy tissue and an animal model of injected astrocytomas. We are also characterizing the anti-tumor properties of various cannabinoid compounds in these models. Our broad, long-term goal is to understand the molecular mechanisms underlying immune surveillance in the brain and the biology of microglial cell activation in the presence of brain tumors.
This research should provide novel insight into the pathogenesis of brain tumors and open alternative therapeutic avenues.
Susan Ferguson, Ph. The overall goal of my research program is to use a multi-level approach, combining molecular biology, anatomy, genetics and behavioral neuroscience, to understand the role of cortico-basal ganglia circuitry in the development of behaviors that are associated with drug reward and addiction, as well as in the processes that underlie decision-making, motivation and impulsivity. To accomplish these goals, my laboratory employs a novel chemical-genetic approach that uses viral vectors to express artificial, engineered G-protein coupled receptors known as DREADD receptors in discrete neuronal cell populations in rodents.
Activation of DREADD receptors by the otherwise inert synthetic ligand clozapine-N-oxide will lead to transient alterations in neuronal activity either increasing or decreasing cell function depending on which G-protein coupled DREADD receptor is expressed of the targeted cell populations. This neuronal modulation can be paired with specific phases of the behaviors that we study, including psychostimulant-induced behavioral sensitization, drug self-administration and operant learning tasks, in order to parse out the neural circuitry that contributes to behaviors associated with addiction and other neuropsychiatric disorders.ns1.rootguards.com/christ-in-the-workplace-the-employee-handbook.php
Mechanisms of Action of Different Drugs of Abuse - Oxford Handbooks
Larry Zweifel, Ph. The brain is comprised of numerous discrete nuclei defined by anatomical location, structure, function, and gene expression profiles. Interconnections of the excitatory and inhibitory neurons within and between these structures are the basic components of neural circuits. Electrochemical signals within a circuit generate activity patterns that ultimately provide the substrate upon which the brain performs functional operations.