This study shows the effect of
opiate withdrawal on
dopamine (DA) in the nucleus accumbens (NAC). Microdialysis was used to detect variations in extracellular DA, dihydroxyphenylacetic
acid (
DOPAC) and
homovanillic acid (HVA) in the NAC of freely moving rats during acute and chronic
morphine treatment followed by
naloxone-precipitated withdrawal with and without
clonidine. Basal levels of extracellular DA did not change between sessions, but
morphine (20 mg/kg, i.p.) caused a significant and identical increase in extracellular DA and metabolites in both the acute phase (day 1) and the chronic phase (day 7). On day 8,
naloxone (20 mg/kg i.p.) caused a significant decrease in DA levels accompanied by typical
withdrawal symptoms such as wet dog shakes and teeth-chattering.
Clonidine pretreatment (200 micrograms/kg, i.p.) eliminated both the
withdrawal symptoms and the DA decrease. These results support the view that
morphine increases extracellular DA at times when the
drug is rewarding and also suggest that the converse may be true;
morphine withdrawal decreases DA release in association with the aversive state.