The Neurobiology of Addiction

                                                   by David Marley, Pharm.D.

A person’s initial decision to use alcohol or other drugs (AOD’s) is influenced by genetic, psycho-social, and environmental factors. Once ingested, however, the drug itself can encourage its continued use through direct action on the nerve cells of the brain.

According to Dr.’s Amanda J. Roberts and George F. Koob, the processes that lead to drug seeking behavior and addiction result partly from altered communication among nerve cells, and partly from activation of the brains regions involved in the body’s response to pleasurable stimuli. These researchers postulate that a residual state of craving persists after stopping AOD use, which may promote relapse, even in long term abstainers. Research is beginning to reveal how specific brain regions may be integrated to form neural circuits that modulate aspects of addiction. This knowledge will aid in the development of improved treatment therapies.

Communication among brain cells plays a pivotal role in controlling the body’s functions, including movement, learning and memory, and thought. Accordingly, AOD induced disruption of this communication is the basis for many of AOD’s effects on the body, particularly the brain. Nerve-cell communication is mediated by chemicals that excite or inhibit the impulse-receiving nerve cells (i.e., neurotransmitters) or modify the effects that neurotransmitters have on the impulse receiving cells (i.e., neuromodulators).

In a recent paper, Dr. Gaetano Di Chiara describes the distribution and function of the neurotransmitter dopamine in the brain. Through its actions on the brain’s “reward” center, dopamine may contribute to motivation and reinforcement of alcohol consumption.

Another neurotransmitter affected by alcohol is serotonin. According to Dr. David Lovinger, serotonin levels appear to be lower in the brains of alcoholics than in the brains of non-alcoholics. Serotonin also may promote alcohol’s intoxicating and rewarding effects by interacting with other neurotransmitter systems (i.e. dopamine).

The brain’s major excitatory neuro-transmitter is glutamate. Alcohol inhibits some of the receptors that mediate glutamates actions. These effects may account in part, for the cognitive dysfunction associated with alcoholism.

Another area being researched is alcohol’s effects on gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter, and its main receptor the GABAA - receptor. Enhanced GABA- receptor function may be responsible for alcohol’s sedative effects. Moreover, alcohol induced changes in the GABAA - receptor function may contribute to alcohol dependence and tolerance, and abnormalities in the GABA system may contribute to the predisposition to alcoholism.

Among the neuromodulators affected by alcohol are endogenous opioid peptides. These chemicals may play a significant role in mediating alcohol reinforcement and excessive alcohol consumption. Consequently, medications that interfere with opioid-peptide functioning, such as naltrexone, can be important components of alcoholism treatment.

As pharmacists, we have a responsibility to constantly update our knowledge base on disease states and therapeutics. Today, more than ever, does the analogy apply, that an alcoholic being unable to correctly process alcohol, resembles the diabetic being unable to correctly process sugar. We are at a point now with the research being done in the field of addiction, that it is professionally irresponsible to recognize alcoholism and drug addiction as anything other than a chronic, progressive, and treatable disease.

References:

Roberts,A.; Koob G. The Neurobiology of Addiction. Alcohol Health and Research World,Vol.21, No.2, 101-106, 1997.
Lovinger,D. Serotonin’s Role in Alcohol’s Effects On The Brain. Alcohol Health and Research, World, Vol.21, No. 2, 114-120, 1997.
Gonzales, R., Jaworski, J., Alcohol and Glutamate. Alcohol Health and Research World, Vol.21, No.2, 120-126, 1997.
Mihic,S., Harris, A., GABA and the GABAA - receptor. Alcohol Health and Research World, Vol.21, No.2, 127-131,1997
Froehlich, J., Opioid Peptides. Alcohol Health and Research World, Vol.21, No.2, 132-135, 1997.