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Gamma aminobutyric acid (GABA) is the primary inhibitory neurotransmitter of the nervous system. Some neurons have receptors for this substance on their surface, which allows it to trigger changes in the neuron. The receptors are composed of two subunits, GABA B-R1 and GABA B-R2, and are linked with G proteins, which connect the receptors to potassium or calcium channels in the neuron. GABA inhibits the nervous system by binding with GABA B receptors, which trigger the G proteins to either activate potassium channels and cause them to open, or make it harder for the calcium channels to open, which makes limits the neuron's ability to signal other neurons. GABA B receptors are involved in some psychological and neurological disorders, as well as some types of drug abuse. They may also be connected with memory and the development of the brain.
GABA B receptors are also one of the receptor types with which the drugs GHB and MDMA, or ecstasy, interact. The only specific GABA B agonist drug that was on the market in 2003, baclofen, reduces cravings for cocaine, heroin, nicotine and alcohol in people who are addicted to those drugs. It probably does this by inhibiting the release of the neurotransmitter dopamine in the nucleus accumbens of the brain, a region believed to be involved in the reward circuitry of addiction. Physicians originally prescribed baclofen to treat muscle spasticity in patients tho had spinal cord injuries, multiple sclerosis, cerebral palsy, or Amyotrophic Lateral Sclerosis (ALS). This was because the drug's activation of GABA B receptors inhibits the skeletal muscles' ability to contract.
Baclofen also relieves pain caused by migraine and neuralgias, such as diabetic neuropathy and postherpetic neuralgia, but doctor's don't usually prescribe it because it is a sedative and people develop a tolerance to it quickly. It may also help with some of the symptoms of Parkinson's disease. Scientists have found changes in the GABA B receptors in the brains of Alzheimer's patients, and it also seems to play a role in psychiatric disorders such as depression, anxiety and schizophrenia.
In addition to drugs, changes in GABA B receptors are involved with several disorders of the nervous system. In the early 2000s, scientists discovered that a specific genetic mutation in one of the receptors makes a person far more likely to develop temporal lobe epilepsy, and are more likely to develop severe cases. Drugs that activate the receptors in the peripheral nervous system showed promise as of the 2000s as an option for treating gastroesophageal reflux disease.
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