Academic journal article Alcohol Research

Alcohol, the Brain, and Behavior: Mechanisms of Addiction

Academic journal article Alcohol Research

Alcohol, the Brain, and Behavior: Mechanisms of Addiction

Article excerpt

The actions of alcohol that cause intoxication, initiate and maintain excessive drinking behavior, and promote relapse during abstinence occur primarily in the brain. A thorough understanding of alcohol's effects on the mechanisms underlying brain function is essential to develop and improve alcoholism prevention and treatment strategies. This article is not an exhaustive overview of alcoholism neurobiology, but a sampling of the more significant recent advances in the field. KEY WORDS: neurobehavioral theory of AODU (AOD [alcohol or other drug]use, abuse, and dependence); brain; synapse; neuron; cell signaling; intracellular messengers; protein kinases; phosphorylation; AOD tolerance; AOD withdrawal syndrome.

The specific mental processes thought to underlie the development of alcoholism and its manifestations involve functions such as learning, attention, emotion, and cognition. The normal brain must orchestrate these functions simultaneously to perceive the environment, assess the significance of environmental stimuli in terms of survival, and initiate behavioral reactions. These activities require efficient communication among different regions of the brain and at multiple levels within those regions. This article considers alcohol's effects on three levels of communication within the brain: (1) the synaptic level, involving information transfer between individual nerve cells (neurons); (2) the systems level, representing the integrated activity of different brain regions; and (3) the intracellular level, comprising signaling processes that occur within neurons.

ALCOHOL AT THE SYNAPSE: MODIFYING COMMUNICATION BETWEEN NEURONS

Within the brain, each neuron may communicate with many other neurons. Information is transferred by chemical messengers called neurotransmitters , which are released by one neuron and then bound by specialized proteins called receptors embedded in the outer membrane of another neuron. The tiny gap between communicating neurons is called a synapse. There are many neurotransmitters, each of which binds to a particular receptor. However a given receptor may exist in multiple subtypes. Each subtype may produce a different response to the same neurotransmitter, accounting for multiple effects of the same neurotransmitter in different brain regions or even in different locations on the same neuron (Weiner et al. 1997). Although a given neuron can release only one or two neurotransmitters it may possess different receptors. Thus, a neuron's response to information from other neurons depends on complex interactions of potentially conflicting messages arriving simultaneously (Charness 1990).

One of the most powerful effects of alcohol is to reduce the pace of brain activity in part by (1) decreasing the excitatory actions of the neurotransmitter glutamate at the NMDA subtype of glutamate receptor' and (2) boosting the inhibitory actions of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor (Diamond and Gordon 1997). These actions are among the reasons that alcohol is often thought of as a depressant.

The NMDA and GABAA receptors are linked to ion channels; that is, they function by opening a pore through the cell membrane to allow specific ions (electrically charged atoms) to enter the cell and affect the cells electrical balance (Harris 1999). Other neurotransmitters of interest to alcohol researchers include dopamine, serotonin (5-HT), and a family of substances called opioid peptides. These neurotransmitters interact with their receptors to modulate the activity of the neuron on which they reside.

Dopamine's role in coordinating the execution of complex motor activities has long been recognized. Dopamine also appears to play a major role in motivational behavior (i.e., the pursuit of rewarding stimuli). Alcohol administration causes release of dopamine in a brain region (the nucleus accumbens) that is a key member of a group of linked structures associated with the development of addiction (Rassnick et al. …

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