Tolerance and sensitization induced by ethanol in preweanling rats: effects of the administration of a sequestering agent

CASTELLO, S.; MOLINA, J.C.; ARIAS, C.

Mardel Plata, Buenos Aires

Congreso; XXXII Congreso Anual de la Sociedad Argentina de Neurociencias; 2017

Sociedad Argentina de Neurociencias

Preweanling rats consistently display a locomotor stimulating effect induced by medium-to-high ethanol doses, and we have recently reported that chronic ethanol exposure during the second postnatal week induced tolerance or sensitization to this effect of the drug. Acute locomotion and locomotor sensitization induced by ethanol were difficult to observe in adult heterogeneous rats, which could be associated to differences in ethanol metabolism (acetaldehyde accumulation) at each age. Our goal was to explore the effect of the administration of d-penicillamine (dp), a sequestering agent of acetaldehyde, over the stimulating effect of ethanol after acute or chronic exposure to the drug in two-week-old rats. Firstly, we administrated rats (PD 12) with 2.5 g/kg ethanol, 25 min after being treated with saline or dp (50 or 75 mg/kg). Both dp doses reduced the acute stimulating effect of ethanol. Then we evaluated whether dp administration before each ethanol injection during the chronic exposure phase reduced tolerance and sensitization in two-week-old rats. Results revealed that this treatment did not block these effects, since both phenomena were displayed by pups pretreated with d-penicillamine. These data suggests that acetaldehyde metabolism, along with some neurotransmission systems, is involved in the acute locomotor response of ethanol. In contrast, other factors could be modulating the development and expression of tolerance and sensitization in infant rats.