Activity responses to morphine and amphetamine in rats with elevated NE levels in the pons

The catecholaminergic basis of the stimulant actions of amphetamine and morphine was investigated in adult rats treated neonatally with 6-hydroxydopamine (6-OHDA) to produce depletion of cortical catecholamines and marked elevation of norepinephrine in the pons. On days 3, 5, 7 and 9 after birth, rat pups were injected bilaterally in the lateral ventricles with 100, 200, or 400 micrograms of 6-OHDA, dissolved in artificial cerebrospinal fluid (CSF). A control group was injected with the CSF vehicle. The capacity of amphetamine (2 mg/kg) and morphine (1.25, 2.5, and 3.5 mg/kg) to produce behavioral stimulant effects was then subsequently tested in adults. The stimulant effect of amphetamine was attenuated in animals pretreated with 100 and 200 micrograms 6-OHDA and was blocked in those treated with 400 micrograms 6-OHDA. The stimulant effects obtained with morphine were blocked by all 6-OHDA doses (100 and 200 micrograms). For morphine, no tests were made in the 400 micrograms 6-OHDA group on the basis of results obtained in animals pretreated with the lower doses of 6-OHDA. These results are discussed in terms of differing roles played by the catecholamine systems in the production of behavioral stimulation.