Context- and cue-conditioned potentiation of acute morphine dependence and withdrawal.
Single morphine injections induce a state of acute opioid dependence measured by an increase in naloxone potency to precipitate withdrawal. Repeated morphine exposure (daily/weekly intervals) results in further potentiation of naloxone potency, perhaps due to conditioning mechanisms. The current study tested the hypothesis that previously neutral stimuli could elicit a conditioned potentiation of the withdrawal response following acute bolus injections of morphine. Rats trained on an FR-15 schedule for food received five morphine injections (5.6 mg/kg) at daily intervals. Four hr after morphine injection on Conditioning Days (first 4 days), naloxone (1 mg/kg)-induced suppression of responding was paired either with operant context only, or with a tone/light conditioned stimulus (CS). On Test Day low dose naloxone (0.001-0.33 mg/kg) given 4-h post-morphine preceded the operant session. Rats exposed to naloxone repeatedly in the operant context without CS (Paired-Context Only) showed an increase in naloxone potency on Test Day relative to Unpaired Controls that received all morphine and naloxone in the home cage at a different time of day than operant testing. Rats exposed to the tone/light CS on Conditioning Days also showed a significant increase in naloxone potency relative to Unpaired Controls when the CS was represented on Test Day (Paired-CS), but not when the CS was omitted on the Test Day (Paired-CS/Test Context). Thus, conditioning processes appear to play a significant role in the early development of opioid dependence and withdrawal.
Schulteis
Gery
G
Research Service, VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161-5008, USA. gschulteis@vapop.ucsd.edu
Liu
Jian
J
Amitai
Nurith
N
Tzeng
Sally
S
D000818:Animals; D003216:Conditioning, Operant; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome; D019966:Substance-Related Disorders
D009020:Morphine