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


OBJECTIVE
To determine whether quadazocine would reduce responding for ethanol and sucrose at mu-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 mu-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.
Williams
K L
KL
Department of Psychology, University of Michigan, Ann Arbor 48109-0632, USA. keithwil@umich.edu
Pakarinen
E D
ED
Woods
J H
JH
D000428:Alcohol Drinking / Q000523:psychology; D000818:Animals; D001392:Azocines / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004327:Drinking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D008253:Macaca mulatta; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects; D012054:Reinforcement, Psychology; D012646:Self Administration; D013395:Sucrose / Q000494:pharmacology
D001392:Azocines; D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D000431:Ethanol; D013395:Sucrose; D009271:Naltrexone; D010622:Phencyclidine; C035969:quadazocine