Differential effects of drug conditioned stimuli on in vivo dopamine transmission in the nucleus accumbens shell and core of morphine sensitized rats.

Stimuli conditioned (CS’s) by pavlovian association with drugs of abuse are thought to play an important role in the acquisition, maintenance and relapse of drug dependence. Previous studies of our group showed that presentation of a CS, Fonzies Filled Box (FFB), increased extracellular dopamine (DA) in the nucleus accumbens (NAc) shell of morphine and nicotine-conditioned rats, as compared to control rats, and failed to affect DA transmission in the core. Morphine (1 mg/Kg sc) or nicotine (0.4 mg/Kg sc) given 40 min after CS presentation increased extracellular DA in the shell of drug conditioned rats to a larger extent than control rats. Morphine also increased DA in the core but no differences with control rats were observed. In this study we monitored by microdialysis the responsiveness of DA transmission in the two different compartments of NAc, the shell and the core, to morphine conditioned stimuli in morphine sensitised rats. Four experimental groups were compared: morphine-conditioned and saline-conditioned morphine sensitised rats, morphine-conditioned and saline-conditioned controls rats. Presentation of CS increased DA in the shell of both sensitised and control morphine-conditioned rats, and in the core of sensitised morphine-conditioned rats. Post hoc test revealed a larger increase of DA in the shell and core of sensitised morphine-conditioned rats compare to the other groups. Morphine injection (1 mg/Kg sc) after FFB presentation increased DA in the shell of all groups. Post hoc test revealed a lesser increase of DA in the shell of sensitised morphine-conditioned rats. Subcutaneous morphine injection preferentially increase DA in the NAc core of sensitised groups, compare to control groups. In conclusion, sensitisation differentially affected DA responsiveness to the drug-CS and to the drug itself in the shell and in the core of the NAc.