Importancia dopaminérgica en farmacodinamia de cocaína evaluada por alteraciones de GABA y glutamato en el núcleo accumbens de ratas

Abstract

The aim of the present study was to investigate the role of dopamine in cocaine pharmacodynamics in rats. To test this hypothesis, we measured GABA and glutamate level changes in the accumbens nucleus. This approach is supported by the preponderance of evidence which has consistently shown alterations in dopaminergic activity after cocaine administration. Furthermore, GABA and glutamate have considerable irnportance in cocaine's acute and chronic effects. The relationship between GABA and glutamate with dopaminergic activity in the nucleus accumbens is well-known. A 16-day study was designed for the administration of cocaine chlorhydrate (IP) at 30 mglkglday increasing by 5 mglkglday each 4 days to animals which had been stereotaxically injured in the nucleus accumbens with 6-OH-dopamine (6-OHDA) neurotoxin dissolved in ascorbic acid. A base group was formed which received ascorbic acid diluted in 0.9% saline solution stereotaxically in the nucleus accumbens, and was treated with an equal volume of 0.9% saline solution (IP). The control group received 6- OHDA (diluted in ascorbic acid) stereotaxically in the nucleus accumbens and was given 0.9% saline solution as treatment. GABA and glutamate levels were determined by enzymatic assays. The results of this work show a significant decrease of GABA levels in the group that received chronic cocaine administration in comparison to the base and control group. Glutamate levels were significantly higher in the cocaine group than in the base group, but not significantly different from the control group. In conclusion, the results of the present work suppofi the idea of the great irnportance of dopaminergic activity in cocaine pharmacotherapy. This dopamine role could be either through GABA or glutamate level alterations or both. Direct action of increased cocaine level on the so-called reward system could be another explication.