Attenuation of alcohol drinking in tetrahydroisoquinoline-treated rats by morphine and naltrexone.

In rats of either the Sprague-Dawley or Long-Evans strain, either tetrahydroisoquinoline (THP) was infused chronically ICV, or one of three protoberberine (PBN) compounds was administered subcutaneously at birth. When the animals were 120-180 days of age, a constant concentration of alcohol was offered simultaneously with water to those rats which demonstrated a clear-cut preference for alcohol. This concentration was selected on the basis of an alcohol preference screen. After alcohol intakes had stabilized, naltrexone was injected subcutaneously in a dose of either 1.0 or 5.0 mg/kg twice a day for three consecutive days. The higher dose (10.0 mg/kg total) of naltrexone suppressed the voluntary intake of alcohol by 26%, whereas the lower dose (2.0 mg/kg total) attenuated alcohol drinking by 14%. Both doses of naltrexone reduced food intake but did not appreciably affect water intake or body weight. When morphine was injected according to the same regimen in a dose of 10.0 or 2.5 mg/kg twice per day, a 49% reduction in alcohol intake was produced by the higher dose and a 32% decline followed the lower dose. Although morphine attenuated food intake, neither water intake nor body weight was affected. Saline control injections administered twice daily in the same way failed to alter any of the intake measures or body weight. These findings indicate that the long-lasting opiate antagonist naltrexone attenuates the voluntary consumption of alcohol in a manner similar to that produced by naloxone. The present results are discussed in terms of the evidence that an opiate agonist and antagonist may exert their actions by different mechanisms in the brain, possibly through separate subpopulations of opiate receptors.