DRUG ABUSE The Chemical Changes Induced by Drugs in the Brain

Certain characteristics seem to be common to all abuse-inducing drugs:

• The craving is similar to all those that produce dependence, although different drug groups show different physiological and behavioral effects
• Environmental factors influence not only the acute effect of the drug but, also the probability of an eventual dependence, as well as relapsing in it.
• There is a genetic predisposition to dependence.
• Following continuous exposition to the drug, the craving for it increases although, in many cases, the drug’s capacity to induce euphoria gradually decreases.
• For many drugs, craving does not happen during withdrawal syndrom, but when the drug’s maximal effect begins to wane.

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.