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![Neurotransmitters on the Synapse Velázquez-Soto, Karla Irenisse, RISE Program University of Puerto Rico, Cayey, Puerto Rico 00736 ______________________________________________________________________________ Abstract Neurotransmitters worked on the synapse in a manner that has both sides positive and negative. In drug addiction, specially, a neurotransmitter roles proceeds sympathetic that correspond to energy generation that inhibits digestion and parasympathetic promotes calming of the nerves made them digest. Amines, Amino acids and neuropeptides are the most important and influenced neurotransmitters that manipulated psychostimulant addiction on neurons. In addition, these drugs were self-administered intravenously, and then located into loci, a cerebral part that establish order and recollect memorial content. Exist many hypotheses about how they work and its possible find a treatment using same neurotransmitters that were caused drugs abuse. However, any of these hypotheses were proved with animals only, no with humans. Hopefully, in a near future can use it techniques to control psychostimulant addiction. Table of Contents Introduction Autonomic Nervous System Neurotransmitters Synapses Psychostimulant Addiction Dopamine and other Neurotransmitters ______________________________________________________________________________ Introduction Autonomic Nervous System The nervous system is engaged within any organ into our bodies. By the way, this is needed to comprehend every movement of the neurotransmitters on different synapses. Basically, the Autonomic Nervous System, knew as ANS, is part of peripheral nervous system which controls many organs and muscles, most times, by a manner involuntary and reflexive. However, can be conscious such as breathing; even thought, almost 75% of the organs and muscles like heart rate, digestion, salivation, diameter of the pupils, urination and sexual arousal. This “controlling machine” of our bodies divided by two subsystems: parasympathetic, sympathetic nervous system. (Reference No. 10 on the list) Autonomic Nervous System: Red = Sympathetic; Blue = Parasympathetic (Autonomic Nervous System, Google images 2008) Parasympathetic nervous system promotes calming nerves to regulate function, in other words, is a “rest and digests” response. An appropriate parasympathetic activity mediates digestion and consequence the absorption of nutrients. Also constrict such muscles like pupil, lens and bronchiolar diameter when is needed oxygen. Cardiac nerves, also impart within parasympathetic control of heart and myocardium. Sympathetic nervous system works as “flight or flight” response that uses energy generation to inhibit digestion. For example, Dilates pupils and relaxes the lens, allowing more light to enter the eye, accelerates heart rate and promotes contractively of cardiac cells to providing a mechanism to enhance the blood flow. Definitely, parasympathetic and sympathetic systems works in opposition, however, are complementary one to each other. Mean while, sympathetic system accelerates any function, the parasympathetic system takes a break. This is like blood pressure in the heart, were the difference systolic and diastolic pressure is that systolic is when the heart valves contraction and the diastolic is when the heart releases. Is important to mention that these two subsystems that works on the autonomic nervous system are complementary with neurotransmitters that involves non-adrenergic and non-cholinergic pathways. Non-cholinergic neurons are neurotransmitters that release acetylcholine. This pathway concentrated in specific regions of the brainstem and thought to be involved in cognitive functions, especially memory. Acetylcholine neurotransmitter works on parasympathetic nervous system and such drugs can change cholinergic activity blocking their respective receptors. Nor-adrenaline neurons increase the level of excitatory activity within the brain. Nor-adrenergic pathways are involved in the control of functions such as attention and arousal. These neurons have a important role in sympathetic nervous system, therefore, drugs easily causes changes in functions ranges as the effects in monoamine neurotransmitters receptors. Neurotransmitters Neurotransmitters are the chemicals which allow and moderate the transmission of signals from one neuron to the next across synapses. They are also found at the axon endings of motor neurons, where they stimulate the muscle fibers. They are packaged into synaptic vesicles that are located on the pre-synaptic zone, the axon. Later, are released into the synaptic cleft, where they bind to receptors in the membrane on the post-synaptic zone, the dendrite. Identify a neurotransmitter is a process that establish different properties. A chemical considered as a neurotransmitter when: the chemical is present in the pre-synaptic vesicle, are sufficient quantity in the pre-synaptic neuron to affect the post-synaptic dendrite, and are post-synaptic receptors to that chemical. Neurotransmitter can be amino acids, amines, and neuropeptides, which are shows in the table below. Small molecule neurotransmittersTypeNeurotransmitterPostsynaptic effectAcetylcholineExcitatoryAmino acidsGamma amino butyric acid (GABA)InhibitoryGlycineInhibitoryGlutamateExcitatoryAspartateExcitatoryBiogenic aminesDopamineExcitatoryNor-adrenalineExcitatorySerotoninExcitatoryHistamineExcitatory Neuropeptide neurotransmittersCorticotropin releasing hormoneCorticotropin (ACTH)Beta-endorphinSubstance PNeurotensinSomatostatinBradykininVasopressinAngiotensin II Another particular characteristic about neurotransmitters function is how they can works as excitatory or inhibitory one. This characteristic is identified when the neurotransmitters passes between the action potential stage (voltage like waves or energy used) to the dendrite. Excitatory neurotransmitter increase the probability that the target cell will fire an action potential and inhibitory neurotransmitter decrease this probability. Therefore, exist neurotransmitters that have both characteristics and effects; everything depends on the properties of the neurotransmitter and the reaction of this into the dendrites receptors. Synapse Synapse is a space between the pre-synaptic and post-synaptic zones that allows neurons to form circuits within the central nervous system, to connect to and control other systems of the body. A typical neuron gives rise to several thousand synapses; all depends of what type of neuron was. For example, synapses can connect axons to axons, axons to dendrites or dendrites to dendrites. Basically, the transition of the neurotransmitters has several parts beginning from a chemical synapse between an axon of one neuron and a dendrite of another. The electrical impulses arriving at the axon terminal triggers the release of neurotransmitters vesicles, which diffuse across the synaptic cleft to receptors on the adjacent dendrite temporarily affecting the likelihood that an electrical impulse will be triggered in the latter neuron. Once released the neurotransmitter is rapidly metabolized or is pumped back into a neuron, after a specialized enzyme digest the no functional neurotransmitters. Neurotransmitters-Transition (Neurotransmitters, Google images) Psychostimulant Addiction, Experimental Evidence As mentioned before, nervous system controls all parts of the body, including organs, muscles and all the interactions between them. Definitely, neurotransmitter and the synapses parts are the beginning of all these reactions, not just into the organs, also on possible consequences if the neurotransmitters interactions failed like anxiety, irritability, emotion, mood, motivation, appetite, sexual activity, aggression and others. As is on our knowledge, these consequences are similar to the drugs abuse too, or as is called in this review psychostimulant addiction. This is one of the most problems of the society because isn’t be illegal drugs addiction, is be to any medicines, any anti-depressives and any MD prescription. Neurotransmitters as dopamine, serotonin, cholinergic and many others are completely involved into psychostimulant addiction. In the last years many scientists still studying how can manage the psychostimulant addiction starting change the neurotransmitters range. Dopamine (DA) and Others Neurotransmitters Dopamine receptors have an important role into drug addiction. Almost all addictive drugs like cocaine, nicotine, opiates, marijuana and ethanol increase DA levels on the loci. Therefore, any of these drugs are located on the loci or are administrated intravenously, inhibiting DA receptors on the dendrites. According to Gardner (2008), DA levels were increased by the reversal DA transporters to the pre-synaptic stage, causing euphoria and immediately caused psychostimulant addiction to the drug exposed. He proved in animals that exists two pharmacological strategies to manipulate DA neurotransmitters transmission and antagonist the abuse. The first strategy was to modulate DA receptors and the latter one was to modulate DA transporters. His study was with a derived of a Chinese herb called Stephanie (THP), he proved that is a non-selective D1 or D2 receptor antagonist and THP can be used as a pharmacotherapy against heroin abuse. When the cocaine or heroin enters to the DA loci altered the electrical BSR, but Gardener (2008) used THP as a substitution of cocaine doing an inhibition on the D1 and D2 dopamine receptors. As a result, he blocked loci and decreased the cocaine and heroin addiction, modulating DA receptors. Another similar study with opiates by Spector (1998), demonstrated the theory of pharmacotherapy in monoamines, like dopamine; as said Spector (1998) and cited: “The results presented here demonstrate that systemic administration of levamisole reduced the symptoms of naltrexone-induced morphine withdrawal, produced a significant increase in the levels of endogenous morphine and codeine in brain and peripheral organs, and significantly altered the metabolism of the monoamine neurotransmitters in specific brain regions…”. Basically, she proved that immunostimulant Levamisole can increase the morphine and codeine (opiates) levels. She and her co-workers did their bases on the discovered of (Goldstein et al. 1985) that identified the presence of synthesized morphine and codeine into mammalian tissues. First Spector (1998), chose two groups of rats, where the experimental group was treated with morphine and codeine. Five days later she took the experimental group and extracts the morphine and codeine using the high performance liquid chromatography (HPLC) to separate the chemicals. Later, she analyzed the monoamines neurotransmitters metabolites in lung, heart, colon and spleen. The results from these proceeds were the addictive rats to opiates decreased their dependence when the Levamisole were injected. Definitely, Levamisole doesn’t just work with bacteria and virus diseases, also increased the levels of morphine and codeine on monoamines neurotransmitters, as a manner to controlling the psychostimulant addiction to opiates. Olive (2007), did a study about the learning relevance for addiction on Glumate neurotransmitter. He specified that Glumate is the most abundant neurotransmitter on the synapses because it works with any drugs that interact into dopamine transporters and receptors. He proved that the association between drugs and specific environmental cues becomes overlearning and these types of overlearning lead drug craving and relapse. This repetition resulting in attenuates the Glumate transmission at the same time controls the abuse to drugs. Conclusion Different scientists still studying with a great emphasis the different strategies described before however were just hypothesis. These studies were just proved with animals like rats, but no with humans. Even thought, many of the articles used in this review establish that were in process, for example, people that were addicted to marijuana are be treated with methadone in substitution to marijuana and heroin Gardener (2008) mentionded on his experiment that: “The former strategy has – to date – primarily utilized DA receptor antagonists, while the latter strategy has – to date – primarily utilized indirect DA receptor agonists that can be viewed as pharmacologically substituting for the addictive psychostimulants in a manner analogous to methadone substitution for heroin.”. The methadone work as an inhibitor on specific DA receptors and is expected that with a certain time these persons can attenuates their psychostimulant addiction. Inclusive, governments as Puerto Rico and United States are paying this treatment to addicted people. In another point of view, these mechanisms can be used in a future in other types of psycho-stimulation. 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