Direct applications of cocaine to the striatum via microdialysis probes produced a concentration-dependent increase in dopamine overflow, while applications to the amygdala were ineffective. Amphetamine was also considerably more potent in the striatum, suggesting differences in DA transporters in the two brain region Cocaine was found to increase striatal ACh in both anesthetized and unanesthetized rats. Morphine, at 10 mg/kg, also elevated striatal ACh. MK-801 at low doses (0.1 mg/kg), on the other hand, produced a modest decrease in extracellular levels of the transmitter. Applications of cocaine to the hippocampus produced a concentration-dependent increase in extracellular NE. In the frontal cortex, on the other hand, only the highest concentration (100 MU-m) produces an increase in extracellular NE. Systemic administration of cocaine (20 mg/kg i.p.) produced no effect on extracellular NE in either the hippocampus or frontal cortex. The differential effects of cocaine in the two regions may suggest differences in the affinity of cocaine for the NE uptake sites. Fluoxetine applied focally to the frontal cortex and raphe increased extracellular 5-HT. A concurrent decrease of 20% in 5-HT occurred in each normally perfused region following focally applied fluoxetine at the other site. Systemic fluoxetine increased 5-HT in the raphe but decreased it in the frontal cortex. The net effect of systemic fluoxetine appears to be determined predominantly by increased 5-HT in the somatodendritic region, which inhibits raphe firing, resulting in a decrease in cortical release. Electrical stimulation of the VTA as well as injections of enkephalin into this region produced increases in the nucleus accumbens DA and locomotor activity. These two effects appeared to be dissociated.
