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Negative reinforcing properties of naloxone in the non-dependent rhesus monkey: influence on reinforcing properties of codeine, tilidine, buprenorphine, and pentazocine.

Scheduled infusions of naloxone (1-100 micrograms/kg/inf.) and of buprenorphine (250 micrograms/kg/inf.) generated drug avoidance behavior in the non-dependent rhesus monkey under a continuous avoidance-escape paradigm. Pentazocine (1-100 micrograms/kg/inf.) codeine, (1-100 micrograms/kg/inf. and tilidine (1-250 micrograms/kg/inf.) were ineffective. Addition of varying doses of naloxone to scheduled infusions of codeine, tilidine, and pentazocine generated avoidance behavior not present with scheduled infusions of these opioids alone. The naloxone doses necessary for generation of avoidance behavior were low with the agonists codeine and tilidine, higher with the weak antagonist pentazocine, and highest with the strong antagonist buprenorphine. When monkeys were presented with the fixed tilidine-naloxone combination (100 + 8 parts) and pentazocine-naloxone combination (100 + 1 part) and the buprenorphine-naloxone combination (100 + 66 parts) presently in clinical use only the tilidine-naloxone combination generated drug avoidance behavior to an appreciable extent.

Animals↗

Acute alcohol intoxication paired with aversive reinforcement: ethanol odor as a conditioned reinforcer in rat pups.

Previous research has suggested that infant rats process ethanol sensory properties during acute alcohol intoxication. The present study was designed in order to examine if alcohol odor could act as an aversive conditioned stimulus after the organism experiences the state of intoxication paired with nociceptive stimulation (footshock). In a first experiment 11-day-old pups received intragastric alcohol administration (1.5 g/kg). At different postabsorptive intervals footshock was presented (0-30, 30-60, 60-90, or 90-120 min). An explicitly unpaired control group which experienced footshock prior to the state of intoxication was also employed. All animals were subsequently tested in terms of alcohol intake and ethanol locational odor preferences. Both assessments indicated that pups which were exposed to the unconditioned peripheral stimulus 30-60 min after receiving ethanol expressed strong alcohol aversions. In a second experiment pups were exposed to footshock during this postabsorptive interval. Twenty four hours later, pups experienced ambient ethanol odor paired with soft or rough texture surfaces. Differential texture aversions were registered in experimental animals when compared with controls which suffered the state of intoxication explicitly unpaired with footshock, or unpaired presentations of ethanol odor and the tactile stimuli under consideration. These results appear to support the hypothesis concerning orosensory processing during an acute state of intoxication. Additionally it seems that the hedonic value of sensory attributes of this drug varies as a function of associative processes occurring during such a state.

Alcohol Drinking↗