Dopaminergic neurons in the brain are thought to play an important role in the etiology of schizophrenia. Schizophrenia is thought to be due to an imbalance of dopamine in certain brain areas. The drug cocaine enhances the action of dopamine in the brain. Humans who take cocaine in high doses for a prolonged period of time may suffer symptoms of prolonged depression and apathy similar to the negative symptoms seen in schizophrenics. Similarly, in rats the repeated administration of high doses of cocaine can produce a decrease in locomotor activity and a lack of the usual sensitization state seen with lower dose stimulant drug challenge. In earlier studies, we evaluated the effects of cocaine administration on the uptake of dopamine in three brain areas of the rat. These data will be published in the July 1994 issue of the Journal of Pharmacology and Experimental Therapeutics. We found that chronic cocaine administration produced a significant decrease in the uptake of dopamine into the frontal cortex (49%) with no significant differences in the nucleus accumbens or striatum. Baseline locomotor activity was significantly lower (29%) in rats treated chronically with cocaine compared with saline-treated rats. A challenge dose of cocaine or d- amphetamine produced similar increases in locomotor activity above the corresponding baseline values in both saline- and cocaine-treated rats, indicating that behavioral sensitization had not occurred. We have continued our work in this area by asking the question """"""""does the lack of behavioral sensitization correlate with the decrease of dopamine uptake in the frontal cortex?""""""""

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002598-04
Application #
5203769
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code