ETHANOL-MEDIATED APPETITIVE REINFORCEMENT AND BEHAVIORAL STIMULATION IN INFANT RATS IS INHIBITED BY AN ACETALDEHYDESEQUESTERING AGENT

PAUTASSI RM; NIZHNIKOV ME; SPEAR, N.E.

Paris, France

Congreso; 2010 International Society for Biomedical Research on Alcoholism (ISBRA) World Congress; 2010

International Society for Biomedical Research on Alcoholism (ISBRA)

Ethanol’s motivational consequences affect the progression from controlled toproblematic drinking. Exposure to ethanol early in life is yet another factor thatfacilitates this transition. Recent studies revealed appetitive reinforcement inpreweanling (infant) rats given pairings between 1.0 g/kg ethanol and salient tactilecues. It has been suggested that at least part of the motivational effects of ethanolcan be attributed to acetaldehyde, a metabolic product of ethanol oxidation. Ethanolinducedactivation in mice is blocked by systemic administration of d-penicillamine(DP), a drug that sequesters acetaldehyde. The present study aimed at assessing therole of acetaldehyde in the motivational effects of ethanol in infant rats. In Experiment1 pups (postnatal days 13-14, PD 13-14) were given d-penicillamine (0, 25, 50 or 75mg/kg) 35 min before pairings of 1.0 g/kg ethanol (ig; unconditional stimulus, US) anda rough surface (sandpaper, conditioned stimulus, CS). At test, pups given sandpaperethanolpairings exhibited greater preference for the CS than unpaired controls,but only if they did not receive the acetaldehyde-sequestering agent. Pre-trainingadministration of 25 or 50 mg/kg DP completely blocked the expression of ethanolmediatedappetitive conditioning. D-penicillamine treatment did not alter ethanol intake(as measured in the consumption-off-the floor test) and blood ethanol levels at timeof conditioning were also unaffected by DP injections. Experiment 2 tested ethanolinducedactivation in a novel environment in thirteen-day old infants given systemic (0,25, 50 or 75 mg/kg; ip) or central (intra-cisterna magna injections, volume: 1 μl, dose:0 or 75 μg) administration of DP. Pups treated with ethanol (1.25 g/kg, ig) exhibitedsignificantly more motor stimulation during the rising limb of the blood ethanol curvethan vehicle-treated controls. This effect was not affected by systemic treatment withDP. Central administration of DP, however, significantly decreased ethanol-inducedbehavioral activation in the novel environment. These results fit well with previous datasuggesting that: (a) infant rats are highly sensitive to the reinforcing effect of ethanol,and (b) that this motivational effect is associated with the activating effects of the drug.Novel information provided by our study is that both effects seem to be mediated bythe first metabolite of ethanol, acetaldehyde.