Does scopolamine block the development of ethanol-induced behavioral sensitization?

Abstract

Background: The cholinergic system is important in learning processes and probably influences behavioral sensitization to drugs. This study examined the effects of scopolamine (scop), a muscarinic antagonist, on the behavioral sensitization to ethanol (EtOH) stimulant effect in mice.

Methods: In experiments 1 and 2, male Swiss albino mice received saline or 1.0 mg/kg scop (s.c.) + saline or EtOH (i.p). (1.0 g/kg in experiment 1 and 2.2 g/kg in experiment 2), for 21 days. Locomotor activity (LA) was recorded once a week, being the treatment withdrawn for 7 days after the last test. On the 28th day (challenge 1), they were evaluated under saline or EtOH. In experiment 2, 3 days after the first challenge, they were tested in an open-field arena, under saline or 2.2 g/kg EtOH. Three days after this, mice were tested under saline or 1.0 mg/kg scop in the activity cages.

Results: Acutely, EtOH and scop did not alter the LA. However, when both drugs were coadministered, a significant reduction was observed. During the treatment, tolerance to the depressor effect was developed and behavioral sensitization observed only in the saline + 2.2 EtOH group. In challenge 1, the groups scop + 1.0 EtOH, saline + 2.2 EtOH, and scop + 2.2 EtOH presented higher levels of LA than that of the control groups. However, in challenge 2, conducted in a different setting, no differences between groups were observed. In challenge 3, when the animals received scop, both groups pretreated with 2.2 g/kg EtOH (saline + 2.2 EtOH and scop + 2.2 EtOH groups) presented higher levels of activity suggesting an interaction between EtOH and scop.

Conclusions: Although the coadministration of scopolamine had impaired the observation of sensitization on the 21st day test, when the group scop + EtOH was challenged with scop + EtOH, it seems that the scop just masked the observation, but did not impair the development, of the EtOH-sensitization observed in the challenge with EtOH alone. The higher levels of LA in groups pretreated with EtOH only in the cages but not in the open-field arena confirm the importance of environmental factors, such as the context of drug administration and testing.