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

Rationale: The endogenous opioid system may mediate the reinforcing effects of ethanol as well as sweet-tasting solutions. For example, opioid antagon ists, such as naltrexone;reduce ethanol- and sucrose-reinforced responding in rhesus monkeys. If these effects are due to blockade of the Fr-receptor, then an opioid antagonist such as quadazocine with a receptor selectivity profile similar to that of naltrexone should reduce responding at doses cor related with its mu-selectivity. Objectives: To determine whether quadazoci ne would reduce responding or ethanol and sucrose at mu-selective doses, an d whether quadazocine and naltrexone would reduce responding for a bitter-t asting drug solution such as phencyclidine. Methods: Rhesus monkeys were gi ven access to ethanol, sucrose, or phencyclidine Concurrently with water. P rior 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 aff ecting the concurrently available water. Quadazocine reduced the fluid deli veries of both phencyclidine and water when concurrently available. Naltrex one reduced only phencyclidine fluid deliveries. Conclusions: The opioid an tagonist effect on oral-reinforced responding is not selective for ethanol or sweet-tasting solutions; responding for phencyclidine was reduced as wel l. Quadazocine and NTX may reduce responding by blocking the mu-receptor be cause the relative potency of these antagonists to reduce oral self-adminis tration was similar to their relative potency to produce withdrawal in morp hine-dependent monkeys. However, water responding was low in these experime nts, and thus we cannot rule out rate-dependent effects of the antagonists.