{"id":3824,"date":"2015-03-21T10:38:15","date_gmt":"2015-03-21T10:38:15","guid":{"rendered":"http:\/\/ivbar4u.com\/blog\/addictioneducation\/?p=3824"},"modified":"2015-03-21T10:38:15","modified_gmt":"2015-03-21T10:38:15","slug":"molecular-mechanisms-of-methamphetamine-induced-neurotoxicity","status":"publish","type":"post","link":"http:\/\/ivbar4u.com\/blog\/molecular-mechanisms-of-methamphetamine-induced-neurotoxicity\/","title":{"rendered":"Molecular Mechanisms of Methamphetamine Induced-Neurotoxicity"},"content":{"rendered":"

Methamphetamine<\/a> is a stimulant that is also highly soluble in water and affects the CNS<\/a> most. Categorically it fits in the group of synthetic drugs chemically related to amphetamine but it has more adverse effects on the Central nervous system than the parent compound. Abuse of these illegal psychostimulants<\/a> has become an international public health problem, with an estimated 14 to 52 million amphetamine-type stimulant users worldwide, exceeding the total number of cocaine abusers and second only to the number of cannabis abusers. This number has continued to rise in spite of the fact that much has been done to publicize the adverse effects these amphetamine related stimulants are linked to. Meth or speed as known in stimulant use circles exists in different forms like powder, tablets and capsules. It can also be found in a purer crystalline form.<\/p>\n

It\u2019s dangerous why is it used?<\/a><\/h2>\n

Just like most stimulants or drugs that are known to induce euphoric feelings, methamphetamine is also taken for similar reasons for example; to induce euphoric feelings, increased sense of well-being, increase energy and to calm anxiety. Being a powerful drug its effects are felt immediately after the use but these effects can last for long hours. They may be accompanied by acute adverse effects such as increased blood pressure and heart rate, which may cause irreversible damage to blood vessels in the brain, resulting in cerebrovascular accidents, stroke, and death. Methamphetamine also produces hyperthermia, pupil dilation, flushing, tremors, trismus and bruxism, muscle tension, loss of appetite or anorexia, and loss of pleasure in food intake which further leads to deterioration of the user\u2019s health.<\/p>\n

\"methamphetamine\"<\/p>\n

Effects of Methamphetamine<\/a><\/h1>\n

Being an addictive drug<\/a>, after a prolonged use the users may develop tolerance. It\u2019s most common symptoms after a prolonged use include; temporomandibular joint syndrome<\/a>, dental erosion, and myofacial pain. Long-term use also produces lack of appetite, weight loss, accelerated aging, nose-bleeding problems, nonhealing wounds, tooth decay and fracture known as \u201cMeth mouth\u201d. Psychiatric symptoms include anxiety, depression, increased aggression, social isolation, psychosis, mood disturbances, and psychomotor dysfunction. Long periods of high consumption can cause paranoid psychosis. Other symptoms of chronic methamphetamine use may also include; deficits in attention, working memory, and decision making. Most addicts are stuck in the use of meth as a result of the withdrawal symptoms which include the following; irritability, fatigue, impaired social functioning, and intense craving for the drug. Researchers have given evidence that the negative neuropsychiatric consequences of methamphetamine abuse are due, at least in part, to drug-induced neuropathological changes in the brain. Although the exact molecular mechanisms of neuronal body loss are not known, there is evidence to suggest the coexistence of different types of cell death, including apoptosis and necrosis ; indicated by the morphology of neurons stained with hematoxylin-eosin. \u00a0Growing evidence exhibits that methamphetamine and MDMA<\/a> induce an increase in lipid peroxidation and DNA oxidation<\/a> as well as increased levels of oxidative stress markers such as hydroxyl radical producing neurotoxicity. Methamphetamine increases expression of inducible nitric oxide synthase (nNOS<\/a>)\/ neuronal nitric oxide synthase (iNOS<\/a> ) indicating increased synthesis of neuronal nitric oxide, which combines with superoxide radicals to form peroxynitrite which is a strong oxidant and a major neurotoxin . Induction of nNOS\/iNOS by methamphetamine or MDMA\u00a0 constitutes part of the mechanism of methamphetamine damage, as selective inhibition or genetic inactivation of nNOS and overexpression of cupper zinc superoxide dismutase (CuZnSOD), an enzyme that catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide, prevent methamphetamine neurotoxicity . Even though methamphetamine increases iNOS expression in the striatum , there is no basis for supposing the involvement of glial nitric oxide in methamphetamine-induced toxicity, but it is interesting to note that mice deficient in iNOS have increased resistance to methamphetamine-induced dopamine neuron damage.<\/p>\n

\"methamphetamine\"<\/p>\n

The neurotoxic effects of methamphetamine on the dopaminergic system are accompanied by activation of astroglia and microglia in the same areas\u00a0 being strongest in the striatum, the area with biggest toxicity. Glial cells are not activated in the nucleus accumbens, which is not much damaged . In mice, glial activation in striatum and in substantia nigra occurs shortly after methamphetamine administration, as indicated by a significant increase in Mac-1 ;a marker of reactive microglia 24 hours after methamphetamine exposure and prominent increases in GFAP ; a marker of reactive gliosis in response to injury occur within a week \u00a0after treatment . The extent of these glial reactions correlates with the observed severity of neurotoxicity.<\/p>\n

The dopaminergic system is also involved in this toxicity, as demonstrated in various mutant mice in which inactivation of dopamine transport, dopamine D1 receptors or D2 receptors affords a significant protection against methamphetamine toxicity. Administration of THC prevents dopaminergic toxicity after MDMA, a similar amphetamine derivative to methamphetamine, by CB1 receptor stimulation which is present in striatal medium spiny neurons. All these receptors are involved in different aspects of learning processes that became affected by the chronic use of methamphetamine or MDMA.<\/p>\n

Finally, Drug abuse, addiction and independence are problems that people grapple with every day. These problems need to be treated effectively through integrative medicine. Dr. Dalal Akoury (MD) is an expert at this.\u00a0 Call her on (843) 213-1480 for help.<\/p>\n

Molecular Mechanisms of Methamphetamine Induced-Neurotoxicity<\/a><\/h1>\n
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