Dopamine and serotonin imbalances in the left anterior cingulate and pyriform cortices following the repeated intermittent administration of cocaine

Studies on the neurobiology of cocaine abuse suggest that cocaine directly modifies the activity of dopamine neurons projecting from the dopaminc-synt hesizing cells of the ventral tegmental area to the nucleus accumbens. The repeated use of cocaine produces persistent adaptations within the mesocort icolimbic system and the resulting changes in monoamine neurotransmission m ay lead to behavioral sensitization. The present series of experiments soug ht to determine the effects of the repeated, intermittent administration of cocaine for five days on (i) the expression of locomotor activity in respo nse to a cocaine challenge that took place two days after discontinuation o f the pretreatment regimen; (ii) the ex vivo levels of biogenic monoamines, choline and acetylcholine in the nucleus accumbens, the dorsolateral cauda te nucleus, as well as the anterior cingulate, frontal motor, frontal somat osensory and pyriform cortices; and (iii) the degree of neurochemical relat ionship between the left and right hemispheres. The repeated administration of cocaine produced sensitized behavioral responses to a subsequent challe nge. Neurochemical correlates of repeated cocaine administration were obser ved at the cortical level and included a significant decrease in serotonin levels in the left anterior cingulate and pyriform cortices and an increase in dopamine metabolism in the left pyriform cortex. Furthermore, a shift i n the interhemispheric coupling coefficient matrix for dopamine neurotransm ission was observed in both the pyriform cortex and nucleus accumbens of co caine-sensitized animals suggesting that, in these structures, the two hemi spheres are operating independently. These results demonstrate that cocaine produces alterations in specific dop aminergic and serotonergic pathways that arise from the mesencephalon and p roject towards both the anterior cingulate and pyriform cortices. (C) 1999 IBRO. Published by Elsevier Science Ltd.