Repeated nicotine treatment in rats with high versus low rearing activity: analyses of behavioural sensitisation and place preference.

RATIONALE

Repeated treatment with the cholinergic agonist nicotine can sensitise rats to its psychomotor stimulant effects, which is largely due to changes within the mesolimbic and mesostriatal dopamine system. Since this brain system also plays a critical role in motivational processes, changes of motivational functions may also be expected with repeated nicotine experiences.

OBJECTIVE

Our previous work has shown that normal male Wistar rats can differ systematically with respect to rearing activity in a novel open field: animals with high rearing activity (HRA) differed from those with low rearing activity (LRA) with respect to dopaminergic and cholinergic brain activity. In this study, we asked whether HRA and LRA rats might respond differentially to repeated nicotine treatment, which we tested in terms of behavioural sensitisation and place preference.

METHODS

Nicotine hydrogen tartrate (0.4 mg/kg) or saline was administered on eight alternate days (drug treatment). After each injection, the rats had access to one specific quadrant of a circular unbiased place preference apparatus. Sensitisation to nicotine was assessed by measuring locomotion and rearing during drug treatment. On the days after each drug treatment, rats had free access to the entire apparatus without prior drug treatment. Here, we tested for preference for the previously drug-paired quadrant. One week after this procedure, all animals were tested again for sensitisation and place preference after injection of saline or nicotine.

RESULTS

Overall, sensitisation occurred earlier during locomotor than rearing activity. Both, HRA and LRA rats treated with nicotine showed sensitisation, but with different profiles. Rearing sensitised earlier in HRA than LRA rats, and a sensitised locomotor response to nicotine was observed only in HRA rats when compared with baseline. When re-tested again 1 week later, expression of sensitisation to nicotine was detected in rearing and locomotor activity in both HRA and in LRA rats. In the place preference tests, nicotine-treated and saline-treated rats spent more time in the treatment quadrant, but nicotine did not lead to place preference compared to saline. Furthermore, there was no substantial evidence that nicotine might lead to place preference in only HRA or LRA rats. However, we obtained other evidence that HRA versus LRA rats responded differently to the procedure of place preference testing.

CONCLUSIONS

These data supplement previous findings that different levels of psychomotor activity can affect the reactivity to psychostimulant drugs and add new evidence with respect to nicotine.