Locomotor activity: A distinctive index in morphine self-administration in rats

Abstract

Self-administration of addictive drugs is a widely used tool for studying behavioral, neurobiological, and genetic factors in addiction. However, how locomotor activity is affected during self-administration of addictive drugs has not been extensively studied. In our present study, we tested the locomotor activity levels during acquisition, extinction and reinstatement of morphine self-administration in rats. We found that compared with saline self-administration (SA), rats that trained with morphine SA had higher locomotor activity. Rats that successfully acquired SA also showed higher locomotor activity than rats that failed in acquiring SA. Moreover, locomotor activity was correlated with the number of drug infusions but not with the number of inactive pokes. We also tested the locomotor activity in the extinction and the morphine-primed reinstatement session. Interestingly, we found that in the first extinction session, although the number of active pokes did not change, the locomotor activity was significantly lower than in the last acquisition session, and this decrease can be maintained for at least six days. Finally, morphine priming enhanced the locomotor activity during the reinstatement test, regardless of if the active pokes were significantly increased or not. Our results clearly suggest that locomotor activity, which may reflect the pharmacological effects of morphine, is different from drug seeking behavior and is a distinctive index in drug self-administration.

Fig 1. Locomotor activity during morphine self-administration.

(a) The locomotor activity in the morphine SA group was higher than the saline SA group. (b) The infusions in the morphine SA group were higher than the saline SA group. (c) The active pokes in the morphine SA group were higher than the saline SA group. (d) The inactive pokes in the morphine SA group were lower than the saline SA group. ## p < 0.01, ### p < 0.001, compared to saline SA. * p < 0.05, ** p < 0.01,*** p < 0.001, post hoc test compared to saline SA on the same session. Saline SA, n = 8; morphine SA, n = 47.

Fig 2. Locomotor activity in successful or failed acquisition of morphine SA.

(a) The locomotor activity in the successful acquisition group was higher than in the failed acquisition group. (b) The morphine infusions in the successful acquisition group were higher than failed acquisition group. (c) The active pokes in the successful acquisition group were higher than failed acquisition group. (d) The inactive pokes had no significant difference between the successful acquisition group and failed acquisition group. ### p < 0.001, compared to failed acquisition group. * p < 0.05, ** p < 0.01,*** p < 0.001, post hoc test compared to failed acquisition group on the same session. Successful acquisition group, n = 35; failed acquisition group, n = 12.

Fig 3. Locomotor activity was correlated with morphine infusion.

(a) Locomotor activity in the successful acquisition group was correlated with morphine infusion. (b) Locomotor activity in the successful acquisition group was correlated with active pokes. (c) Locomotor activity in the successful acquisition group was not correlated with inactive pokes.

Fig 4. The locomotor activity decreased in the first extinction session.

(a) Compared with the last acquisition, the locomotor activity decreased in the first extinction day (n = 47). (b) The active pokes did not significantly change between the first extinction day and the last acquisition day. (c) The inactive pokes significantly increased in the first extinction day compared with the last acquisition day. (d) The total pokes significantly increased in the first extinction day compared with the last acquisition day. (e) The locomotor activity did not change in the first six extinction days. (f) The active pokes were significantly higher than the inactive pokes in the first six extinction days. * p < 0.05, *** p < 0.001, compared to the last acquisition session. ### p < 0.001, compared to the inactive pokes. && p < 0.01, &&& p < 0.001, post hoc test compared to the inactive pokes on the same session.

Fig 5. Morphine-primed reinstatement resulted in increase of locomotor activity.

(a) Morphine induced reinstatement of drug-seeking behavior (n = 41). (b) Locomotor activity increased in the reinstatement test when compared to the last extinction day. (c) The active pokes in the successful reinstatement group (n = 20) were higher than in the failed reinstatement group on the reinstatement test (n = 21). (d) There was no difference in the inactive pokes between the successful reinstatement group and the failed instatement group. (e) Locomotor activity increased in the reinstatement test for both the successful reinstatement group and the failed reinstatement group. (f) The increase in locomotor activity was not correlated with the increase in active pokes in the successful reinstatement group or the failed reinstatement group. *** p < 0.001, compared to the last extinction session. ### p < 0.001, compared to the failed reinstatement group. &&& p < 0.001, post hoc test compared to the failed reinstatement group on the same session.