MODULATION OF OPERANT SELF-ADMINISTRATION OF ETHANOL BY MU AND DELTA OPIOID RECEPTORS IN TWO-WEEK OLD RATS

MIRANDA-MORALES RS; SPEAR NE; ABATE P

San Francisco, CA, EEUU

Congreso; 35th Annual Scientific Meeting of the Research Society on Alcoholism, June 23-27 -- San Francisco, California; 2012

Research Society on Alcoholism

Opioid control of operant behavior for ethanol reinforcement was tested in 2-week old rats. Although mu opioid receptors are increasingly prevalent during the rat’s first postnatal days, delta opioid receptors are barely noticeable until the second postnatal week. Both have been implicated in ethanol reinforcement in adult rats. Preweanling (infant) rats were trained in an operant learning task to obtain ethanol [5.0%, 7.5%, 10.0% or 15.0%]. Daily training sessions (15 min each) were given on postnatal days (PD) 14–17. All experimental pups rapidly acquired the operant response to gain access to the drug. Significantly more operant responses and greater ethanol intake occurred for 7.5% and 10% than for 5% or 15%. A second experiment analyzed blood ethanol levels (BELs) of animals infused with 7.5 and 10.0% ethanol. Trunk blood samples were obtained immediately after sessions of PDs 15, 16 and 17. BELs achieved when pups were reinforced with 10% ethanol were higher than the ones observed with 7.5% ethanol. BELs were increasing across each daily operant session. In a third experiment, the involvement of mu and delta opioid receptors in ethanol-related operant behavior for 10% ethanol was examined. The protocol was similar to that employed in Experiment 1. In addition, a 15-min extinction session was given on PD18. On PD 16–18, 30- min before operant task, pups were injected ip with CTOP (mu antagonist, 0.1 or 1.0 mg/kg), Naltrindole (delta antagonist, 1.0 or 5.0 mg/kg) or saline. Results indicated that all experimental pups learned the operant response for 10% ethanol on PDs 14–15. During PDs 16–17, experimental pups treated with 5.0 mg/Kg Naltrindole or 0.1 mg/Kg CTOP had significantly less operant responses than controls. These differences persisted throughout extinction session. Results from this study indicate that delta as well as mu opioid receptors are involved in mechanisms of ethanol reinforcement at this early stage of development.