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PNU-99,194
PNU-99,194(A) (or U-99,194(A)) is a drug which acts as a moderately selective D3 receptor antagonist with ~15-30-fold preference for D3 over the D2 subtype. Though it has substantially greater preference for D3 over D2, the latter receptor does still play some role in its effects, as evidenced by the fact that PNU-99,194 weakly stimulates both prolactin secretion and striatal dopamine synthesis, actions it does not share with the more selective (100-fold) D3 receptor antagonists S-14,297 and GR-103,691. In rodent studies, low doses of PNU-99,194 produce conditioned place preference (CPP) with no effect on intracranial self-stimulation (ICSS), whereas low doses of D3 agonists like 7-OH-DPAT inhibit ICSS behavior and cause conditioned place aversion (CPA). In contrast, high doses of PNU-99,194 produce CPA and inhibit ICSS, while high doses of 7-OH-DPAT result in the opposite. Paralleling this, low doses of PNU-99,194 and 7-OH-DPAT induce hyperactivity and hypoactivity, r ...
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D3 Receptor
Dopamine receptor D3 is a protein that in humans is encoded by the ''DRD3'' gene. This gene encodes the D3 subtype of the dopamine receptor. The D3 subtype inhibits adenylyl cyclase through inhibitory G-proteins. This receptor is expressed in phylogenetically older regions of the brain, suggesting that this receptor plays a role in cognitive and emotional functions. It is a target for drugs which treat schizophrenia, drug addiction, and Parkinson's disease. Alternative splicing of this gene results in multiple transcript variants that would encode different isoforms, although some variants may be subject to nonsense-mediated decay (NMD). Function Alpha-synuclein (α-Syn) aggregation via Lewy bodies inclusion, a pathogenic signature exclusively present in PD patients, is decreased by D3 agonists while DA content is elevated by inhibiting DA reuptake and breakdown. The regulation of α-Syn aggregation and clearance enhances brain-derived neurotrophic factor (BDNF) secretion, whi ...
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Mouth
In animal anatomy, the mouth, also known as the oral cavity, or in Latin cavum oris, is the opening through which many animals take in food and issue vocal sounds. It is also the cavity lying at the upper end of the alimentary canal, bounded on the outside by the lips and inside by the pharynx. In tetrapods, it contains the tongue and, except for some like birds, teeth. This cavity is also known as the buccal cavity, from the Latin ''bucca'' ("cheek"). Some animal phyla, including arthropods, molluscs and chordates, have a complete digestive system, with a mouth at one end and an anus at the other. Which end forms first in ontogeny is a criterion used to classify bilaterian animals into protostomes and deuterostomes. Development In the first multicellular animals, there was probably no mouth or gut and food particles were engulfed by the cells on the exterior surface by a process known as endocytosis. The particles became enclosed in vacuoles into which enzymes were secr ...
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Self-administration
Self-administration is, in its medical sense, the process of a subject administering a pharmacological substance to themself. A clinical example of this is the subcutaneous "self-injection" of insulin by a diabetic patient. In animal experimentation, self-administration is a form of operant conditioning where the reward is a drug. This drug can be administered remotely through an implanted intravenous line or an intracerebroventricular injection. Self-administration of putatively addictive drugs is considered one of the most valid experimental models to investigate drug-seeking and drug-taking behavior. The higher the frequency with which a test animal emits the operant behavior, the more rewarding (and addictive), the test substance is considered. Self-administration of addictive drugs has been studied using humans, non-human primates, mice, invertebrates such as ants, and, most commonly, rats. Self-administration of heroin and cocaine is used to screen drugs for possible eff ...
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Memory
Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered, it would be impossible for language, relationships, or personal identity to develop. Memory loss is usually described as forgetfulness or amnesia. Memory is often understood as an informational processing system with explicit and implicit functioning that is made up of a sensory processor, short-term (or working) memory, and long-term memory. This can be related to the neuron. The sensory processor allows information from the outside world to be sensed in the form of chemical and physical stimuli and attended to various levels of focus and intent. Working memory serves as an encoding and retrieval processor. Information in the form of stimuli is encoded in accordance with explicit or implicit functions by the working memory processor. ...
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Learning
Learning is the process of acquiring new understanding, knowledge, behaviors, skills, value (personal and cultural), values, attitudes, and preferences. The ability to learn is possessed by humans, animals, and some machine learning, machines; there is also evidence for some kind of learning in certain plants. Some learning is immediate, induced by a single event (e.g. being burned by a Heat, hot stove), but much skill and knowledge accumulate from repeated experiences. The changes induced by learning often last a lifetime, and it is hard to distinguish learned material that seems to be "lost" from that which cannot be retrieved. Human learning starts at birth (it might even start before in terms of an embryo's need for both interaction with, and freedom within its environment within the womb.) and continues until death as a consequence of ongoing interactions between people and their environment. The nature and processes involved in learning are studied in many established fi ...
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Anxiolysis
An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiety disorders and their related psychological and physical symptoms. Nature of anxiety Anxiety is a naturally-occurring emotion and an innate response of the body to the environmental stimuli. Mild to moderate anxiety would increase level of performance. However, when anxiety levels exceed the tolerability of a person, anxiety disorders may occur. People with anxiety disorders can exhibit fear responses such as defensive behaviors, high levels of alertness and negative emotions, without external stimuli which induce anxiety within an individual. Those with anxiety disorders are also often found to have concurrent psychological disorders, most commonly depression. Anxiety disorders are divided into 6 types in clinical recognition. They are ...
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Hypothermia
Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe hypothermia, there may be hallucinations and paradoxical undressing, in which a person removes their clothing, as well as an increased risk of the heart stopping. Hypothermia has two main types of causes. It classically occurs from exposure to cold weather and cold water immersion. It may also occur from any condition that decreases heat production or increases heat loss. Commonly, this includes alcohol intoxication but may also include low blood sugar, anorexia and advanced age. Body temperature is usually maintained near a constant level of through thermoregulation. Efforts to increase body temperature involve shivering, increased voluntary activity, and putting on warmer clothing. Hypothermia may be diagnosed based on either a person ...
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Nociception
Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the sensory nervous system's process of encoding noxious stimuli. It deals with a series of events and processes required for an organism to receive a painful stimulus, convert it to a molecular signal, and recognize and characterize the signal in order to trigger an appropriate defense response. In nociception, intense chemical (e.g., capsaicin present in Chili pepper or Cayenne pepper), mechanical (e.g., cutting, crushing), or thermal (heat and cold) stimulation of sensory neurons called nociceptors produces a signal that travels along a chain of nerve fibers via the spinal cord to the brain. Nociception triggers a variety of physiological and behavioral responses to protect the organism against an aggression and usually results in a subjective experience, or perception, of pain in sentient beings. Detection of noxious stimuli Potentially damaging mechanical, thermal, and chemical stimuli are detected ...
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Receptor (biochemistry)
In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a receptor and cause some form of cellular/tissue response, e.g. a change in the electrical activity of a cell. There are three main ways the action of the receptor can be classified: relay of signal, amplification, or integration. Relaying sends the signal onward, amplification increases the effect of a single ligand, and integration allows the signal to be incorporated into another biochemical pathway. Receptor proteins can be classified by their location. Transmembrane receptors include ligand-gated ion channels, G protein-coupled receptors, and enzyme-linked hormone receptors. Intracellular receptors are those found inside the cell, and include cytoplasmic receptors and nuclear receptors. A molecule that binds to a receptor is called a ligand ...
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Postsynaptic
Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie perception and thought. They allow the nervous system to connect to and control other systems of the body. At a chemical synapse, one neuron releases neurotransmitter molecules into a small space (the synaptic cleft) that is adjacent to another neuron. The neurotransmitters are contained within small sacs called synaptic vesicles, and are released into the synaptic cleft by exocytosis. These molecules then bind to neurotransmitter receptors on the postsynaptic cell. Finally, the neurotransmitters are cleared from the synapse through one of several potential mechanisms including enzymatic degradation or re-uptake by specific transporters either on the presynaptic cel ...
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Autoreceptor
An autoreceptor is a type of receptor located in the membranes of nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or hormones released by the neuron on which the autoreceptor sits. Similarly, a heteroreceptor is sensitive to neurotransmitters and hormones that are not released by the cell on which it sits. A given receptor can act as either an autoreceptor or a heteroreceptor, depending upon the type of transmitter released by the cell on which it is embedded. Autoreceptors may be located in any part of the cell membrane: in the dendrites, the cell body, the axon, or the axon terminals. Canonically, a presynaptic neuron releases a neurotransmitter across a synaptic cleft to be detected by the receptors on a postsynaptic neuron. Autoreceptors on the presynaptic neuron will also detect this neurotransmitter and often function to control internal cell processes, typically inhibiting further release or ...
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Locomotor Activity
Animal locomotion, in ethology, is any of a variety of methods that animals use to move from one place to another. Some modes of locomotion are (initially) self-propelled, e.g., running, swimming, jumping, flying, hopping, soaring and gliding. There are also many animal species that depend on their environment for transportation, a type of mobility called passive locomotion, e.g., sailing (some jellyfish), kiting (spiders), rolling (some beetles and spiders) or riding other animals (phoresis). Animals move for a variety of reasons, such as to find food, a mate, a suitable microhabitat, or to escape predators. For many animals, the ability to move is essential for survival and, as a result, natural selection has shaped the locomotion methods and mechanisms used by moving organisms. For example, migratory animals that travel vast distances (such as the Arctic tern) typically have a locomotion mechanism that costs very little energy per unit distance, whereas non-migratory animal ...
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