A Surprising Linkage between A Brain Chemical, Sleep Drugs, and Brain Injury

In the brain, neurons (nerve cells) form long interconnecting chains that carry signals. These chains may be 10 neurons long or 100 neurons long. Let’s call a neuron at one end of the chain “neuron A,” which squirts a chemical into a tiny gap between it and its neighbor, “neuron B,” that causes it to transmit an electrical impulse down the chain to “neuron C.” Neuron “C” then itself releases a chemical onto “neuron D,” and in this way an impulse travels along the chain of neurons. The gaps between neurons are called synaptic junctions, or just synapses. The chemicals released by neurons that act on other neurons in the chain are called neurotransmitters.

A key neurotransmitter goes by the acronym GABA. When released from one neuron onto another, GABA inhibits the ability of that neuron to carry an impulse. Benzodiazepine drugs (Valium, Xanax, Lorazepam, etc.) have a special affinity for GABA receptors on neurons. When these drugs bind a specific site on GABA, they cause the neurotransmitter to slow down synaptic transmission and thus they have a sedative effect. Benzodiazepine drugs are prescribed to relieve anxiety, suppress convulsions, and relax muscles on a short-term basis.

Not long ago, a person with insomnia might be prescribed a low-dose benzodiazepine drug. Now insomniacs have Ambien and Lunesta, which are less addictive, safer to use, and are less tolerance producing. Their mechanism of action is to bind loosely to GABA receptors and provide sufficient short-lasting sedation to provide a good night’s sleep. Some people experience side effects to these new drugs, such as headache, nausea, vertigo, and amnesia. The drugs must be used with caution, for several users have ended up wandering around at night or driving their car without recalling their exploits the next day. Geriatric patients have fallen after using them, but on the whole, their sedative effects can allow one to dreamily follow a sleep-inducing luna moth as it flits out the window of your bedroom (as in the television commercial). It is best to use sleep-inducers in moderation.

A recent discovery links GABA receptors and Ambien (chemical name “zolpidem”) in an unexpected way. There is evidence that after administering Ambien to patients with brain injuries, or even to comatose patients in a vegetative state, some may arouse and behave in a “normal” way for a number of hours, after which they slip back into non-responsiveness. The Ambien treatment does not work for all brain damaged patients, but when it does work it seems like a miracle. In Israel, a 50-year-old woman had a brain injury and was in a coma. After taking Ambien she regained the ability to speak and feed herself, but after three to four hours she would revert to her comatose state. The effect was repeated on a daily basis. A patient in the U.S. had been in a vegetative state for three years and was constantly screaming. After treatment, he stopped screaming and reacted appropriately to scenes on television, even laughing at funny episodes. Much research needs to be done before scientists understand exactly how Ambien interacts with GABA to produce such results. Dr. John Whyte, at the Moss Rehabilitation Research Institute in Philadelphia, is launching a federally-funded program to better understand the Ambien-GABA linkage.

Sources: New Scientist, May, 2006; http://www.sleepeducation.com, May 6, 2012; http://www.nytimes.com/2011/12/04/magazine; http://www.philly.com/2/22/12/news; other sources; and thanks to Kathy.