THE ROLE OF ACETALDEHYDE IN ETHANOL REINFORCEMENT ASSESSED THROUGH CLASSICAL CONDITIONING IN RAT NEONATES

MARCH, S.M.; ABATE P.; SPEAR N.E.; MOLINA J.C.

Atlanta, Georgia

Congreso; 34th Annual Scientific Meeting of the Research Society on Alcoholism; 2011

Research Society on Alcoholism

Acetaldehyde (ACD) is a biologically active metabolite of ethanol capable of producing ethanol-like effects such as anxiolysis, conditioned-place preferences and conditioned taste aversions. It has also been shown that adult rats and mice will self-administrate large amounts of this metabolite directly into the brain. Nizhnikov et al (2007) found that intracysternal administration of ethanol supports appetitive conditioning in newborn rats. This phenomenon was completely blocked when the central catalase system was inhibited through sodium-azide. In the present study, d-penicillamine –a sequestering agent capable to form stable abducts with ACD- was used in order to directly analyze ACD reinforcement in newborn pups. Cesarean-delivered rat pups were subjected to a pavlovian conditioning procedure. Subjects received a central administration of d-penicillamine (75ug in experiment 1 and 40 ug in experiment 2) or vehicle. Five minutes later, lemon odor (conditioned stimulus, CS) was associated with ethanol (100 mg %) or acetaldehyde (0.35 umol) administered in the cysterna magna (volume: 1ul). One hour later, pups were tested with an artificial nipple delivering water in the presence of lemon odor. The suckling response was delineated as: total time spent on the nipple, mean grasp duration (total time divided by number of grasps), total number of disengagement from the nipple and, percent body weight gain (measure of fluid intake). In Experiments 1 and 2, EtOH and ACD exerted positive reinforcing effects. Centrally administrated ACD, as well as EtOH, associated with the CS, increased the duration of attachment bouts in comparison with neonates that received an IC administration of vehicle. A similar profile was observed in terms of total time of attachment. Additionally, d-penicillamine inhibited EtOH and ACD reinforcing effects. These results support the notion that central ACD represents a critical factor for the establishment of EtOH's reinforcing effects in neonatal rats. It is interesting to note that in perinates, the activity of the central catalase system is considerably higher than in older animals. It is possible that differential levels of ACD production during the course of ontogeny, implies differential sensitivity to EtOH's unconditioned properties. The present results argue in favor of heightened sensitivity to EtOH' reinforcing effects within a stage in development where ACD production is probably higher than latter in life.