Does scopolamine block the development of ethanol-induced behavioral sensitization?
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 Locomotor activity (LA) was recorded once a week, being the treatment withdrawn for 7 days after the last test.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.
Takahashi
Shirley
S
Departamento de Psicobiologia, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil.
Fornari
Raquel Vechio
RV
Quadros
Isabel Marian Hartmann
IM
Oliveira
Maria Gabriela Menezes
MG
Souza-Formigoni
Maria Lucia Oliveira
ML
D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D012601:Scopolamine / Q000494:pharmacology*
D002492:Central Nervous System Depressants; D018727:Muscarinic Antagonists; D000431:Ethanol; D012601:Scopolamine