Introduction: Withdrawal period from abused substance is accompanied by many
problems. In some addicted people, relapse to drug-seeking and compulsive abuse develops.
On time intervention may reduce relapse in some addicted people by knowing underlying
Methods and Materials: In this study 48 rats were randomly divided into four groups: pair,
isolation, withdrawal pair, and withdrawal isolated. Rats in withdrawal groups after one week
for acclimatization were first induced for morphine addiction by injection of increasing dose of
morphine (5 mg/kg/rat in the first day to the final dose of 35 mg/kg/rat) for 7 days and then
were withdrawn from morphine by the injection of naltrexone (3 mg/kg/rat) in 8 days. In control
groups no treatment was applied. On day 14, rats in all groups were first evaluated for
avoidance memory and novelty-seeking behavior. Then rats in day 15 were sacrificed and
brain immediately removed for the assessment of oxidative stress (OS) status in the
hippocampus and prefrontal cortex for malondialdehyde (MDA), glutathione and nitrite/nitrate.
Results: Avoidance memory was better in withdrawal pair rats. Novelty-seeking behavior
was increased in withdrawal isolated rats. Anxiety was reduced in withdrawal isolated rats.
MDA was higher in withdrawal isolated rats. Glutathione and nitrite/nitrate were higher in
withdrawal isolated rats.
Conclusion: Pair state (socialization) improves avoidance memory, increases anxiety and
reduces novelty-seeking behavior in withdrawal period. Also, oxidative stress markers responded
differently to withdrawal stress in isolated and pair rats.