Dopamine is a neurotransmitter that is used by the brain to convey messages related to wakefulness, concentration, appetite, motivation, memory and feelings of reward. Dopamine agonists are drugs that increase or mimic the activity of dopamine such that the brain perceives and responds to the action of the drug in much the same way it does to dopamine itself. Narcolepsy is a sleep disorder characterized by disordered regulation of the REM sleep state and excessive daytime sleepiness, or EDS.
Identification
Narcolepsy is a rare primary sleep disorder of the central nervous system that affects between 0.03 and 0.05 percent of people in the United States. Symptoms of the disease typically first appear in patients aged 15 to 25 years. The primary complaint is EDS. Many narcoleptic patients also suffer from cataplectic attacks that cause temporary loss of muscle tone, often in response to strong emotion. Hypnagogic illusions are also symptomatic of narcolepsy, causing a person to have a vivid dreamlike experience at the onset of sleep. This is often paired with sleep paralysis, which renders the muscles immovable despite a conscious state of mind.
Cause
Many scientists hypothesize that narcolepsy is an autoimmune disorder in which the body's immune cells attack a specific population of cells in the hypothalamus of the brain that make a neurotransmitter called hypocretin. These findings are supported by the fact that the cerebral spinal fluid of many patients diagnosed with narcolepsy is free of hypocretin molecules.
Hypocretins
Hypocretin-producing neurons in the brain function to stimulate other neurons within the brain -- namely those neurons involved in maintaining a long period of wakefulness. Mice and dogs that do not make any hypocretin molecules have been bred for scientific research; these animals exhibit many of the same symptoms seen in humans suffering from narcolepsy, further supporting the role of this neurotransmitter in the pathology of the disease.
Treatment
EDS is often the most bothersome symptom of narcolepsy and can cause accidents if the sufferer has the tendency to fall asleep behind the wheel of a car or while operating machinery. For this reason, narcolepsy is treated with drugs that promote wakefulness, including modafinil, amphetamines and methylphenidate. If cataplexy is also bothersome, the patient may be given prescriptions for tricyclic antidepressants or sodium oxybate.
How Dopamine Agonists Help
Drugs that mimic or increase the activity of dopamine seem to help in the treatment of EDS in patients suffering with narcolepsy. Presumably this is due to the fact that narcoleptic patients are deficient in hypocretin neurotransmitters and thus are unable to excite dopaminergic neurons that are involved in maintaining wakefulness on their own. Dopamine agonists are essentially able to bypass the hypocretin signaling mechanisms required to excite dopaminergic neurons, helping patients to feel more awake.
References
- "Molecular Neuropharmacology" ; Nestler, Hyman, and Malenka; 2009
- "Sleep Disorders in Neurology: A Practical Approach"; Sebastiaan Overeem and Paul Reading; 2010
- National Institute of Neurological Disorders and Stroke: Narcolepsy Fact Sheet
- "Sleep and Sleep Disorders: A Neuropsychopharmacological Approach"; Malcolm Lader et al.; 2006
