Kindling in alcohol withdrawal

Abstract

In many alcoholics, the severity of withdrawal symptoms increases after repeated withdrawal episodes. This exacerbation may be attributable to a kindling process. Kindling is a phenomenon in which a weak electrical or chemical stimulus, which initially causes no overt behavioral responses, results in the appearance of behavioral effects, such as seizures, when it is administered repeatedly. Both clinical and experimental evidence support the existence of a kindling mechanism during alcohol withdrawal. Withdrawal symptoms, such as seizures, result from neurochemical imbalances in the brain of alcoholics who suddenly reduce or cease alcohol consumption. These imbalances may be exacerbated after repeated withdrawal experiences. The existence of kindling during withdrawal suggests that even patients experiencing mild withdrawal should be treated aggressively to prevent the increase in severity of subsequent withdrawal episodes. Kindling also may contribute to a patient's relapse risk and to alcohol-related brain damage and cognitive impairment.

Figure 1

Graphic representation of the kindling concept during alcohol withdrawal. The term “kindling” refers to the phenomenon that people undergoing repeated cycles of intoxication followed by abstinence and withdrawal will experience increasingly severe withdrawal symptoms with each successive cycle.

Figure 2

Possible mechanisms contributing to kindling during alcohol withdrawal. Repeated binge drinking followed by abstinence leads to repeated withdrawal episodes, resulting in increasingly severe alterations of brain functions. The alterations include (1) a progressive imbalance between suppressive (i.e., inhibitory) and stimulating (i.e., excitatory) influences (i.e., neurotransmission) on brain function, (2) disturbances in certain hormonal systems (i.e., neuroendocrine dysregulation), and (3) other neurochemical perturbations. The changes result in increasingly severe withdrawal symptoms, including seizures, anxiety, toxic effects on nerve cells (i.e., neurotoxicity), and altered perception of alcohol’s effects. Any of those symptoms may increase the patient’s potential for relapse and vulnerability to brain damage. GABA_A receptor: A receptor for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). NMDA receptor: A receptor for the excitatory neurotransmitter glutamate. HPA axis: A hormone system involving hormones produced in the hypothalamus, pituitary gland, and adrenal gland. Voltage-operated Ca²⁺ channel function: These calcium channels are located on the outer surface of the nerve cell. Electrical activity causes the channels to open, admitting calcium. Calcium entering the cell regulates many important processes related to cellular communication. ⇑ indicates an increase and ⇓ indicates a decrease in the brain function or withdrawal symptom listed. to increased seizure susceptibility upon cessation of alcohol exposure.