Ethanol-Induced Conditioned Place Preference In Infant Rats Is Inhibited By Opioid Antagonists

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

San Diego, CA, USA

Congreso; 32a Reunión Científica Anual de la Research Society on Alcoholism (RSA); 2009

Research Society on Alcoholism (RSA)

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:ES-MX; mso-fareast-language:ES-MX;} @page Section1 {size:612.0pt 792.0pt; margin:72.0pt 90.0pt 72.0pt 90.0pt; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> ETHANOL-INDUCED CONDITIONED PLACE PREFERENCE IN INFANT RATS IS INHIBITED BY OPIOID ANTAGONISTS RM Pautassi, ME Nizhnikov, NE Spear State University of New York at Binghamton, Center for Developmental Psychobiology, Binghamton, NY, USA, 13902-6000.   Ethanol reinforcement is a key factor in the transition from controlled drinking to abuse and dependence. Sensitivity to ethanol reinforcement early in life may further increase the likelihood of these alcohol-related problems. A recent study (Nizhnikov et al., 2008) revealed appetitive reinforcement in preweanling (infant) rats given low-dose ethanol. Conditioned place preference was found following 1.0 but not 2.0 g/kg ethanol and only when the drug was delivered through intragastric intubation (but not when using intraperitoneal injections). The present study employed the latter experimental preparation to analyze the role of the endogenous opioid system in ethanol reinforcement. Opioid antagonists reliably decrease alcohol intake in adult rats and inhibit ethanol conditioned reinforcement in neonate rats. In Experiment 1 infant rats (postnatal days 14-15, PD 14-15) were given a general opioid antagonist (naloxone, 0.25, 0.75 or 1.5 mg/kg) thirty-five minutes before pairings of 1.0 g/kg ethanol (unconditional stimulus, US) and a rough surface (sandpaper, conditioned stimulus, CS). At test (PD 16), pups given sandpaper-ethanol pairings displayed greater preference for the CS than unpaired controls, but only if they did not receive the opioid antagonist. Pre-conditioning injection of 0.75 or 1.5 mg/kg naloxone dramatically abolished expression of ethanol-mediated appetitive conditioning. The lowest naloxone dose (0.25 mg/kg) had an intermediate effect. To further scrutinize the mechanisms underlying ethanol reinforcement, Experiment 2 tested ethanol place conditioning in infants treated with CTOP (mu opioid antagonist; 0.10 or 1.0 mg/kg), naltrindole (delta opioid antagonist, 1.0 or 5.0 mg/kg), or saline followed by ethanol-sandpaper pairings (1.0 g/kg). Pups treated with saline exhibited significantly greater sandpaper preference at test than unpaired controls or paired pups treated with either CTOP or naltrindole. Conditioned responding by ethanol was completely inhibited in pups given either of these opioid antagonists prior to CS-US pairings. These results replicate previous data (Nizhnikov et al., 2008) of reliable appetitive reinforcement by ethanol in infant rats. Perhaps more important, they also agree with previous research (Nizhnikov et al., 2006) in suggesting a putative role for the opioid mu and delta family receptors in supporting ethanol-mediated motivational learning early in life.