The Role Of Nucleus Accumbens In Drug-priming And Foot-shock Stress Induced Reactivation Of Extinguished Conditioned Place Preference

Objective High rate of relapse to drug using behavior after a long period of abstinence characterizes the behavior of experienced addicts . This renders relapse the primary problem for the treatment of addiction. Without thorough understanding of the factors that determine recurred craving and drug-seeking, it would be unlikely for drug health care professionals to provide effective treatment. Factors that most powerfully trigger the relapse to drug-using behavior in humans are re-exposure to drug, exposure to stress, or re-exposure to stimuli that have been previously associated with the reinforcing properties of drugs. The mechanisms involved in the reinstatement of self-administration paradigm by stress and drug priming are still not clear. Some researchers suggested that the mesolimbic dopaminergic system (with the dopaminergic neurons located in the ventral tegmental area and its projection terminated in the nucleus accumbens) was involved in both procedures. However, up to date there has been no study addressing the neural basis of the reactivation of place preference. We investigated the role of nucleus accumbens in thereactivation of place preference (as an indication of drug-seeking behavior) induced by drug-priming or footshock. To validate the possible involvement of mesolimbic dopaminergic pathway in this reactivation, lesions were placed at nucleus accumbens and ventral tegmental area to verify whether they are involved in drug-priming or footshock-triggered reactivation of conditioned place preference.Methods (1)Psychical dependence model were set up with male rats by trained with morphine(10mg/kg, sc.)through a conditioned place preference paradigm(8 sessions of daily pairing of morphine with one of the two compartments). (2)Twenty rats were randomly assigned into 2 groups, with ten each group. One of the groups was trained with morphine while the other with saline as control. They were tested for place preference 1, 3, 5, 7, 9, 11, 13 and 15 days after the last drug-pairing session, respectively. (3)After rats were successfully trained with through a conditioned place preference paradigm. Ncleus accumbens or ventral tegmental area was lesioned with a direct current(DC) passing through the location. After a 15-day abstinence period, random intermittent footshock (DC square wave, 0. 5mA, 0. 5s width, off time 10-70s)or drug priming(morphine 1mg/kg,sc.)was given and the place preference score was recorded. Result (1)Within the 8-day discipline rats began to develop preference from the third day and this trend was seriously strengthened during the next 5 days and saturated in 5-th or 6-th day. The longest preference time was about 1 Ltnin. (2)After the last drug-pairing session, rats showed similar degree of preference to the drug-pairing room land 3 days after training. However, this place preference became weaker at the 5th day and fell to the same level on the 13th and 15th day as the respective saline control groups. The morphine-induced conditioned place preference woulddisappear 13 days after the last drug-pairing session in the experimental system we used. (3)A small dose of morphine can trigger reactivation of conditioned place preference in control group. (4)Exposure to random intermittent footshock stress can trigger reactivation of conditioned place preference in control group. (5)In the drug priming reactivation, place preference score of the nucleus accumbens lesion group is significantly lower than sham lesion groups. (6)In the footshock-stress induced reactivation, place preference score of the nucleus accumbens lesion group is significantly lower than sham lesion groups. (7)In the drug priming reactivation, place preference score of the ventral tegmental area lesion group is significantly lower than sham lesion groups. 甀n the footshock-induced reactivation, place preference score of the ventral tegmental area lesion group is not significantly different from the sham lesion groups.Conclusion (1)Injection of morphine can induce conditioned place preference in rats. (2)The morp...