Alterations in the level of neurotransmitters associated with the chronic treatment of antipsychotic drugs.

OBJECTIVE

To investigate the alterations in different neurotransmitters particularly dopamine and serotonin in various regions of rat brain.

METHODS

By using HPLC-ECD, the concentration of dopamine, their metabolites (DOPAC, HVA), serotonin, their precursor (tryptophan), and metabolites (5-HIAA) were determined in different regions such as hypothalamus, cortex, midbrain and striatum. In addition, tryptophan pyrrolase enzyme activity and the concentration of tryptophan were also determined in liver samples, following chronic (21 days I/M) treatment of haloperidol and clozapine (of both commercially available and purified form) in an animal model.

RESULTS

Significant alterations were observed in the level of neurotransmitters in different regions of rat brain. In response to haloperidol treatment, the level of dopamine was observed to be significantly increased in hypothalamus, cortex and striatum but in midbrain the concentration was slightly decreased, While a significant increase (p < 0.05) in the level of serotonin was observed in midbrain, hypothalamus and striatum. However, treatment with clozapine resulted in significant decrease in the level of dopamine in all the regions except cortex; with concurrent decrease observed in serotonin level in all brain regions except cortex where its concentration was slightly increased. Liver demonstrated a significant increase (p < 0.05) in the concentration of tryptophan, however, a slight increase was found in the concentration of brain tryptophan following haloperidol treatment. A marked decrease was observed in the concentration of liver tryptophan, whereas, the brain tryptophan concentration is significantly increased (p < 0.05) in response to clozapine treatment. Marked increase was observed in the tryptophan pyrrolase enzyme activity, plotted against time at the time interval of 15 minutes in response to both haloperidol and clozapine treatment.

CONCLUSION

We suggest that the varying effect of these drugs on neurotransmitter may account for the difference in the consequence profile in response to chronic treatment.