Striatum Methamphetamine Toxicity

March 22, 2015

Methamphetamine Toxicity in the Striatum

The striatum is a crucial part of the brain. This part of the brain plays very important roles but it can be adversely affected by the use of stimulants and other drugs of leisure. Substances such as cocaine and methamphetamine produce their primary effects inside the brain by boosting the presence of dopamine which is a neurotransmitting chemical that activates the pleasure-producing neurons contained within the limbic system. As stated above the limbic system includes the hippocampus, along with several other brain structures. According to the results of two separate studies published in 2008 in the Journal of Neuroscience and Biological Psychiatry, the presence of either cocaine or methamphetamine alters normal adult neurogenesis inside the hippocampus and damages this region’s ability replenish its neuron supply. It is no longer news that methamphetamine intoxication causes long-lasting damage to dopamine nerve endings in the striatum. However the mechanisms underlying this neurotoxicity are not yet known but oxidative stress has been linked to it.

methamphetamine

Microglia are the major antigen-presenting cells in brain and when activated, they secrete an array of factors that cause neuronal damage. Astoundingly, very little work has been directed at the study of microglial activation as part of the methamphetamine neurotoxic cascade. It has been report that methamphetamine activates microglia in a dose-related manner and along a time course that is coincident with dopamine nerve ending damage. Through tests done on mice scientists have discovered that prevention of methamphetamine toxicity by maintaining treated mice at low ambient temperature prevents drug-induced microglial activation. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) not only damages dopamine nerve endings and cell bodies but also causes extensive microglial activation in striatum as well as in the substantia nigra. Contrastingly, methamphetamine causes neither microglial activation in the substantia nigra nor dopamine cell body damage.

Dopamine transporter antagonists do not mimic the effect of methamphetamine on microglia. Hyperthermia, a prominent and dangerous clinical response to methamphetamine intoxication, has been also ruled out as the cause of microglial activation. Together, these data suggest that microglial activation represents an early step in methamphetamine-induced neurotoxicity. Other neurochemical effects resulting from methamphetamine-induced overflow of dopamine into the synapse, but which are not neurotoxic, do not play a role in this response.

Methamphetamine use on the rise despite effects

The use of methamphetamine has been on the rise despite the fact that it is a powerful stimulant drug that has adverse effects when abused as most people do. According to the UN Office on Drugs and Crime reported recently that abuse of amphetamines, including designer drugs such as methamphetamine and 3, 4-methylenedioxymethamphetamine, now exceeds that of cocaine and heroin on a global scale. This presents no sign that its use will decline any soon. Past researchers were able to establish a fact that methamphetamine causes persistent reductions of function in dopamine nerve endings of animals and humans. Methamphetamine neurotoxicity has been under intense study for over 20 years, but still there is much that still remains to be learned about how this dangerous drug causes damage to dopamine nerve endings. The theory that revolves around oxidative stress has been at the top of the speculations. Drug-induced oxidative stress is an attractive construct that can account for many of the effects of methamphetamine on the dopamine nerve ending such as inhibition of tyrosine hydroxylase activity as well as reductions in the dopamine transporter and the vesicle monoamine transporter. This may even be an early event that leads eventually to methamphetamine-induced apoptosis. However, the source of the reactant species that mediate methamphetamine-induced damage is not known.

methamphetamine

Due to their crucial roles they play in mediating the mediating damage to the nervous system, Microglia has attracted considerable attention. Immune like in many ways these interesting cells become activated by damage and then transmigrate to sites of injury where they can secrete an array of factors like cytokines, prostaglandins, nitric oxide, and superoxide that are known to have detrimental effects on neurons. However, the role of microglia in methamphetamine-induced damage to the dopamine system has received little attention. In 1994 a researcher, Bowyer and his colleagues noted for the first time that methamphetamine resulted in activation of microglia in striatum of treated rats. These investigators concluded that microglia were increased in response to nerve ending damage and were not apparently a cause of it. Recently, another research was conducted to give an in-depth analysis of the effect of methamphetamine on striatal gene expression. Numerous genes linked to microglia were activated significantly within hours of methamphetamine intoxication, suggesting the possibility that microglial activation occurs earlier in the methamphetamine toxic cascade than previously thought.

Today there are researchers who are building on the initial analysis of methamphetamine and report the pharmacological characterization of microglial activation by methamphetamine in striatum. As mentioned before, striatum is an area dense in dopamine nerve endings and is known to be targeted for damage by methamphetamine. Microglial activation coincides with the onset of methamphetamine-induced damage in striatum and the extent of this effect is related to the degree of damage to dopamine nerve endings. Numerous nontoxic effects exerted by methamphetamine, such as inhibition of the DAT, increases in synaptic levels of dopamine, activation of D1 and/or D2 DA receptors, and hyperthermia, cannot explain methamphetamine-induced microglial activation.

Finally, this is still a dark area and there is need for more literature so as to establish the mechanism of methamphetamine toxicity on the striatum. Needless to say, 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. Call her on (843) 213-1480 for help.

Methamphetamine Toxicity in the Striatum

GABA Restoration In Addiction Therapy

March 8, 2015

Role of GABA restoration in addiction therapy

There are several drugs of pleasure that people use today. The problem is not exactly in the use of the drugs but rather in the effects they create in the brain. Addiction contrary to what many people think is not a problem with how frequent you take a drug but what even a single puff of or drop of a drug will cause to your brain and the entire nervous system. Composed of the individual nerve cells also known as neurons the nervous system serves as the network in the body. Without this network all communications between the nerve cells will be broken and a person will be incapacitated to even do a simple task as blinking. Typically, nerve signals are transmitted through the length of a neuron as an electrical impulse. When a nerve impulse reaches the end of the neuron it can jump over to the next cell using chemical messengers called neurotransmitters. Therefore without the neurotransmitters the nerves will not be able to send impulses over to other nerve cells in order to initiate specific actions. The neurotransmitters have vital functions in the central nervous system. In the central nervous system these neurotransmitters send impulses between neurons. The functions of the neurotransmitters is not limited to the central nervous system alone but are also crucial in the peripheral nervous system where they send impulses between neurons and gland cells. The peripheral nervous system is composed of nerves that link the central nervous system to the rest of the body.

There are two types of neurotransmitters, the inhibitory transmitters which are known to restore calm in the brain especially after the use of leisure drugs that are known to induce euphoric effects by raising the levels of dopamine and the excitatory neurotransmitters that fires the brain. GABA is one of the inhibitory neurotransmitters that counter the effects of leisure drugs and restores calm in the brain.

GABA restoration

GABA is one of the most abundant neurotransmitters in the central nervous system, and especially in the cerebral cortex. The brain cortex is where thinking occurs and sensations are interpreted. As mentioned above GABA is the primary inhibitory neurotransmitter brain and it helps in tranquillizing stressful, anxious and worrying thoughts. What happens with most drugs of leisure is that they cause instability in the brain leading to anxiety, stress and even depression. These are symptoms of low GABA. Addiction is a cause of low GABA as most drugs deplete GABA. There are several ways through which this can be medically corrected but those with addiction issues usually turn to their drugs as a means of self-medication but this only worsens the situation leading to anxiety and depression. Tranquilizers and downers are no better solutions to low GABA symptoms but finding a safe GABA regulation therapy may help in addiction treatment. The other cause for use of downers and tranquilizers is the rise in the level of norepinephrine. A rise in this neurotransmitter often induces the use of cannabis sativa.

The roles of GABA in the Brain

Made from glutamate in the brain cells, GABA works as an inhibitory neurotransmitter blocking nerve impulses. It is this neurotransmitter that inhibits the actions of dopamine when elevated in level by drug use. Glutamate acts as an excitatory neurotransmitter and when bound to adjacent cells encourages them to fire and send a nerve impulse. However, GABA does the opposite and tells the adjoining cells not to calm, not to send an impulse.

To those with inadequate level of GABA the activities of the excitatory neurotransmitters will not be inhibited and therefore the impulses they send will not be regulated and this often leads to anxiety disorders such as panic attacks, seizures, addiction, Parkinson’s disease and cognitive impairment.

GABA is the most effective neurotransmitter in inhibiting the transmission of nerve impulses from one neuron to another. When this happens it restores calmness in the brain however when drugs are used they inhibit the release of GABA, when GABA release is inhibited there will be more nerve transmissions occurring. These drugs inhibit the release of GABA by causing molecules to bind on neurons near GABA reducing its effect on the neurons. Benzodiazepines and other drugs are known to work in this style, they may also mimic the activities of GABA thereby inhibiting its transmission.

GABA rESTORATION

Need For GABA restoration in addiction Treatment

After a long term use of certain drugs, the level of GABA will be depleted to a point where it will be at an all-time low. This will lead to myriad of complications as the nerve impulses will be unregulated. This will lead to such problems as anxiety, depression, cognitive impairment and seizures among other diseases. Without restoring the level of GABA to healthy limits, any attempt to treat an addict will be ineffective.

Finally, Drug addiction treatment is a complex procedure that needs the input of an experienced integrative doctor. the health of neurotransmitters matters a lot and now that it is known that some drugs depletes these neurotransmitters there is need for treatment of addiction in a manner that restores the functions of the entire nervous system. This is why here at AWAREmed we are dedicated to finding the best solutions to addiction and dependence on substances. Dr. Dalal Akoury (MD) is always in the mood of helping any patient to be addiction free. Do not hesitate to call on her for help in managing any sort of chronic pain as well as other diseases.