Chunk #23 — RESULTS — Reductions in responding for ethanol after GABAAR α4 subunit knockdown are present when testing occurs at the time of maximal knockdown and require ethanol reinforcement
Because the mRNA reduction occurs within a relatively short interval of days, it is possible that ongoing ethanol self-administration during the time period from day 5 to day 18, when the expression of the GABAAR α4 subunit was changing, somehow impacted the results obtained at day 18. To test whether the GABAAR α4 subunit mediates the reinforcing effects of ethanol when testing begins at a point when α4 is at or near its maximal decrease, rats were trained to lever press for 20% ethanol and infused with the Ad-NSS or Ad-shα4 virus as above. However, testing did not commence until the 18th day (instead of the fifth day) after viral infusion, a day at which we have shown maximal reductions in α4 subunit expression occur (Rewal et al. 2009). On the test day, responding by one-half of the rats was reinforced with ethanol; responding by the second half of the rats was not reinforced. If the decrease in responding following Ad-shα4 infusion into the NAc shell depends upon actual delivery of the ethanol reinforcer, then responding should be decreased only in the group receiving ethanol and not in the second cohort in which responding was unreinforced.
