NIH conference. Alcohol withdrawal and noradrenergic function.
Alcohol withdrawal syndrome is characterized by signs of overactivity of the sympathetic nervous system. Biochemical studies indicate that increased release of norepinephrine is associated with certain symptoms of alcohol withdrawal, and the severity of the withdrawal symptoms correlates positively with the amount of norepinephrine released. In the rat, the brain epinephrine concentration is reduced by alcohol, a phenomenon probably associated with both the intoxicating and rewarding effects of alcohol intake. Furthermore, intoxicating effects of alcohol can be reversed by inhibiting epinephrine synthesis in the rat brain. In this species, alcohol withdrawal is associated with profound depletion of epinephrine in the hypothalamus. When clonidine, a norepinephrine alpha-2-receptor agonist, was infused in alcoholics, these receptors were found to be subsensitive during alcohol withdrawal, and this subsensitivity may contribute to the syndrome. Repeated withdrawals may lead to "kindling" and thus further enhancement of noradrenergic overactivity. Pituitary responsiveness to corticotropin-releasing hormone, which is a central regulator of stress responses and increases the firing rate of brain noradrenergic neurons, is altered during alcohol withdrawal.
Linnoila
M
M
National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Mefford
I
I
Nutt
D
D
Adinoff
B
B
D000437:Alcoholism / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003000:Clonidine; D003346:Corticotropin-Releasing Hormone; D004837:Epinephrine / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007696:Kindling, Neurologic; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D011942:Receptors, Adrenergic, alpha; D003346:Corticotropin-Releasing Hormone; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine