Antagonist-precipitated opioid withdrawal in rats: evidence for dissociations between physical and motivational signs.
In rats made opioid dependent by the implantation of a single morphine 75 mg base pellet, an attempt was made to determine whether any correlational existed between physical and motivational withdrawal signs by adjusting the dose of naloxone used to precipitate withdrawal. The models used to study motivational signs were taste (one- and two-bottle) conditioning and operant responding for food under an FR15 schedule of reinforcement. Naloxone at doses of 0.01 mg/kg and above produced both a conditioned taste aversion (two-bottle test only) and reduced food responding in morphine pellet, but not placebo pellet, implanted animals. No physical withdrawal signs, e.g., wet dog shakes, diarrhoea, were noted until naloxone doses of 0.05 mg/kg and above were used. It is concluded that the difference in naloxone doses required to elicit physical and motivational withdrawal components provides further support for their dissociation.
Higgins
G A
GA
Addiction Research Foundation, Toronto, Ontario, Canada.
Sellers
E M
EM
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004435:Eating / Q000187:drug effects; D005502:Food; D005508:Food Deprivation / Q000502:physiology; D008297:Male; D009020:Morphine / Q000008:administration & dosage; D009021:Morphine Dependence / Q000503:physiopathology* / Q000523:psychology*; D009042:Motivation; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology* / Q000523:psychology*; D013649:Taste / Q000187:drug effects
D004343:Drug Implants; D009270:Naloxone; D009020:Morphine