Influence of fluoxetine and paroxetine in behavioral sensitization induced by ethanol in mice.
The serotonergic system is involved in depression, anxiety and alcoholism. The rewarding properties of ethanol, mainly its anxiolytic and stimulant effects, as well as the development of dependence on ethanol have been related to the serotonergic system. Consequently, the use of selective serotonergic reuptake inhibitors (SSRI) has been proposed in the treatment of alcoholism. In this study we investigated whether acute administration of the SSRIs fluoxetine or paroxetine is able to (i) reverse the behavioral effects induced by chronic ethanol consumption, and conversely, (ii) to determine whether acute ethanol is able to substitute for the chronically induced behavioral effects of fluoxetine or paroxetine. Four groups of male Swiss mice (n=60/group) received daily i.p. saline, ethanol (2 g/kg), fluoxetine (10 mg/kg) or paroxetine (5 mg/kg) for 27 days. On the 28th day, each group was challenged with saline, ethanol, fluoxetine or paroxetine. The 14 groups (SS, SE, SP, SF, EE, ES, EP, EF, PP, PE, PS, FF, FE, and FS) were then tested in open field, activity cage and plus-maze. EP and EF groups were able to reverse the behavioral sensitization to the psychomotor stimulant effects of chronic ethanol administration. In contrast, a sensitized stimulatory effect was observed in chronically fluoxetine- or paroxetine treated mice challenged with ethanol (PE and FE). An anxiolytic effect was observed whether ethanol was substituted for SSRI or, conversely, SSRI was substituted for ethanol. SSRIs facilitated ethanol-induced locomotor sensitization, although SSRIs by themselves are unable to produce the locomotor stimulation similar to that induced by ethanol. Finally, SSRIs are unable to interfere in the ethanol anxiolytic effect.
Goeldner
F O
FO
Department of Pharmacology, Universidade Federal do Parana, 81531-980 Curitiba, PR, Brazil.
Pigatto
G
G
Ribeiro
A F
AF
Machado
H B
HB
Boerngen-Lacerda
R
R
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D005239:Fear / Q000187:drug effects / Q000523:psychology; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D017374:Paroxetine / Q000494:pharmacology*
D018687:Antidepressive Agents, Second-Generation; D002492:Central Nervous System Depressants; D005473:Fluoxetine; D000431:Ethanol; D017374:Paroxetine