Effects of Acute and Chronic Morphine on DOPAC and Glutamate at Subcortical DA Terminals in Awake Rats

Abstract

Effects of morphine and naloxone on the levels of 3,4-dihydroxy-phenylacetic acid (DOPAC) and glutamate in the striatum and nucleus accumbens of awake rats were studied with in vivo microdialysis. Acute morphine (50 mg/kg, IP) treatment increased the levels of DOPAC and glutamate in the striatum and nucleus accumbens, but both decreased from the elevated levels when naloxone (10 mg/kg, IP) was given 2 h later. Chronic morphine treatment, twice daily for 5 days in incremental doses (5, 10, 20, 40 and 50 mg/kg, IP), increased the level of DOPAC but decreased that of glutamate in the striatum and nucleus accumbens. When naloxone was given 2 h later, the reverse of the above phenomena are found. After given repeated morphine treatment and experiencing naloxone-precipitated withdrawal, the rats with an intact cortex and the rats with ibotenic acid (5 μg/0.5 μl/2.5 min) lesions on the medial prefrontal cortex and sulcal cortex have similar alternations in the levels of DOPAC and glutamate in the striatum. However, in the nucleus accumbens, the level of DOPAC dropped more and the level of glutamate increased more in the intact rats than the lesioned rats during the withdrawal stage. These data suggested that the intact cortex ordinarily exerted an inhibitory role to influence the level of DOPAC in the striatum and nucleus accumbens during chronic morphine treatment. In conclusion, morphine seems to activate different pathways in dependent and non-dependent rats.