The Chemical Changes Induced by Drugs in the Brain
Certain characteristics seem to be common to all abuse-inducing drugs:
Although dependence is a condition common to all drugs, it is easily understandable the great diversity of effects for different classes of drugs, since each class affects different neurotransmitter systems.
In 1993 Robinson and Berridge showed that different kinds of psychostimulant drugs, and drug abuse, induced increase in the extracellular concentration of dopamine in the nucleus accumbens, an area of the mesolimbic dopaminergic system. This increase could be called forth by drugs like cocaine, amphetamine, opiates, alcohol, caffeine, barbiturate, and nicotine.
As described by Nastler (1994) dopamine acts on a G-protein, changing cyclic AMP (cAMP) levels in the nucleus accumbens. Cyclic AMP (cAMP) activates several protein- kinases that regulate transcription factors, like CREB (substances that bind to proteins in response to cAPM). These transcription factors bind to specific DNA areas, promoting increases or decreases in the speed of certain genic transcriptions.
Acute and, mainly, chronic stress play a significant part via the intense liberation of glucocorticoids, well-known for their capacity to increase the nucleus accumbens sensibility to drug-abuse, since they facilitate dopamine release in this nucleus.
The genetic bases of dependence involves multiple genes of the genoma. Activation transcription of the receptor in the dopaminergic system seems to lead to the activation of an specific gene (C-fos), responsible for the activation of the FOS-related protein. This protein may have a neuroadaptive role for the repetitive administration of drugs.
The identification of factors that might confer vulnerability to drug abuse and dependence is helped by new genetic analysis like the manipulation of the molecular genome.
Mind Magazine 3(8), Jan/March 1999
An Initiative by the Center for Biomedical Informatics
Copyright (c) 1998 Universidade Estadual de Campinas, Brasil
Published on 18/Jan/1998