The transfer of rats from a familiar to a novel environment prolongs the increase of extracellular dopamine efflux induced by CCK8 in the posterior nucleus accumbens.

The effects of cholecystokinin octapeptide (CCK8) on extracellular dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, were measured in the nucleus accumbens (N. Acc.). The experiments were carried out using in vivo microdialysis in awake rats submitted, or not, to a novel environment, the four-hole box. The exploratory behavior of the animals was studied concurrently in these boxes and in the elevated plus maze. Without CCK8 treatment, the transfer of animals from their home cages to the four-hole box induced a transient increase in DA efflux and also tended to increase its metabolites in the posterior N. Acc. In rats placed in a familiar environment, the administration of 25 pmol of CCK8 in this region immediately enhanced DA release, with levels rapidly returning to normal at the end of the perfusion. In contrast, this treatment produced a longer effect in rats transferred to the four-hole box, since the DA efflux was still increased 80 min after the removal of CCK8. The intra-accumbal administration of CCK8 induced a hypoexploration in the four-hole box. Moreover, an anxiogenic-like effect of CCK8 was found in the elevated plus maze, only in rats submitted to a novel environment (four-hole box). These data show that (1) the postero-accumbens DA neurons can be activated by environmental changes and (2) that the intensity of the CCK8 effects on extracellular DA levels and on anxiety-like responses seems to depend on the activity of these neurons previous to CCK8 treatment. The prolonged DA release induced by CCK8 in animals placed in a new situation could correspond to a biochemical anticipation preparing them to react when faced by another stimulus.