Dihydroetorphine: physical dependence and stereotypy after continuous infusion in the rat.
In a previous study in this laboratory, exposure of rhesus monkeys to intermittent, high doses of dihydroetorphine for 42 days did not evoke behavioral signs of physical dependence on this opioid either after it was abruptly withdrawn or after challenge with a high dose of naloxone. To investigate further the physical dependence capacity of this opioid, it was given by infusion to rats thereby exposing receptors chronically and continuously to this opioid. Abstinence expressed as body weight loss, irritability, and wet-dog shakes was observed after abrupt withdrawal of the low-dose regimen (5,10, 40 and 40 microg/kg per day for 4 days, respectively). The high-dose regimen (10, 20 and 80 microg/kg per day for 3 days, respectively) produced stereotypy and physical dependence. Although many reported molecular events and dependence studies suggest otherwise, dihydroetorphine's propensity to produce physical dependence, an important determinant of opioid abuse, is real.
Aceto
M D
MD
Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298-0613, USA. maceto@hsc.vcu.edu
Scates
S M
SM
Harris
L S
LS
Ji
Z
Z
D000701:Analgesics, Opioid / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005048:Etorphine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D007263:Infusions, Parenteral; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000523:psychology; D019966:Substance-Related Disorders / Q000209:etiology; D013997:Time Factors
D000701:Analgesics, Opioid; D005048:Etorphine; C034765:18,19-dihydroetorphine