Quadazocine decreases responding reinforced by ethanol, sucrose, and phencyclidine fluid deliveries in rhesus monkeys: comparison to naltrexone’s effects

Abstract

Rationale: The endogenous opioid system may mediate the reinforcing effects of ethanol as well as sweet-tasting solutions. For example, opioid antagonists, such as naltrexone, reduce ethanol- and sucrose-reinforced responding in rhesus monkeys. If these effects are due to blockade of the µ-receptor, then an opioid antagonist such as quadazocine with a receptor selectivity profile similar to that of naltrexone should reduce responding at doses correlated with its µ-selectivity. Objectives: To determine whether quadazocine would reduce responding for ethanol and sucrose at µ-selective doses, and whether quadazocine and naltrexone would reduce responding for a bitter-tasting drug solution such as phencyclidine. Methods: Rhesus monkeys were given access to ethanol, sucrose, or phencyclidine concurrently with water. Prior to the drinking sessions, quadazocine (0.032–3.2 mg/kg) or saline was injected intramuscularly. During the phencyclidine experiment, naltrexone (0.1 and 0.32 mg/kg) was also tested. Results: The highest quadazocine doses (1 and 3.2 mg/kg) reduced ethanol and sucrose fluid deliveries without affecting the concurrently available water. Quadazocine reduced the fluid deliveries of both phencyclidine and water when concurrently available. Naltrexone reduced only phencyclidine fluid deliveries. Conclusions: The opioid antagonist effect on oral-reinforced responding is not selective for ethanol or sweet-tasting solutions; responding for phencyclidine was reduced as well. Quadazocine and NTX may reduce responding by blocking the µ-receptor because the relative potency of these antagonists to reduce oral self-administration was similar to their relative potency to produce withdrawal in morphine-dependent monkeys. However, water responding was low in these experiments, and thus we cannot rule out rate-dependent effects of the antagonists.