TY - JOUR
T1 - Magnitude of opioid dependence after continuous intrathecal infusion of μ- and δ-selective opioids in the rat
AU - Stevens, Craig W.
AU - Yaksh, Tony L.
N1 - Funding Information:
We appreciate the expert and timely manuscript preparation by Ms Ann Johnson and technical assistance by Ms Gall Harty Supported by NIH Grant DA-02110 and Mayo Foundation
PY - 1989/8/3
Y1 - 1989/8/3
N2 - The continuous intrathecal infusion of morphine (2, 6, 20 nmol/h), sufentanil (0.06, 0.2, 0.6 nmol/h), [D- Ala2,MePhe4, Glu-ol5]enkephalin (DAMGO) (0.1, 0.3, 1.0 nmol/h) or [D-Ala2,D-Leu5]enkephalin (DADLE) (2, 6, 20 nmol/h) in unanesthetized rats produces a dose-dependent increase in hot plate latency 1 day after pump implant followed by a gradual return to baseline values by days 3-4, i.e. tolerance. Rats assessed for opioid dependence after 7 days of intrathecal (i.t.) infusion of opioids show a withdrawal syndrome most readily noted by withdrawal body shakes (WBS) after injection of the opioid antagonist, naloxone (1 mg/kg i.p.). The number of WBS was proportional to the infusion dose of opioid agonist. Although each tolerance-producing agent was infused in one of three log-spaced (low, medium, high) doses, selected to have approximately equal antinociceptive activity across agents, the agents varied in the apparent degree of dependence. Thus, at the highest infusion dose, the average number of WBS observed was greatest for DADLE (32.8), morphine (30.2) and sufentanil (25.0) while animals treated with DAMGO displayed a significantly less degree of opioid dependence (8.7).
AB - The continuous intrathecal infusion of morphine (2, 6, 20 nmol/h), sufentanil (0.06, 0.2, 0.6 nmol/h), [D- Ala2,MePhe4, Glu-ol5]enkephalin (DAMGO) (0.1, 0.3, 1.0 nmol/h) or [D-Ala2,D-Leu5]enkephalin (DADLE) (2, 6, 20 nmol/h) in unanesthetized rats produces a dose-dependent increase in hot plate latency 1 day after pump implant followed by a gradual return to baseline values by days 3-4, i.e. tolerance. Rats assessed for opioid dependence after 7 days of intrathecal (i.t.) infusion of opioids show a withdrawal syndrome most readily noted by withdrawal body shakes (WBS) after injection of the opioid antagonist, naloxone (1 mg/kg i.p.). The number of WBS was proportional to the infusion dose of opioid agonist. Although each tolerance-producing agent was infused in one of three log-spaced (low, medium, high) doses, selected to have approximately equal antinociceptive activity across agents, the agents varied in the apparent degree of dependence. Thus, at the highest infusion dose, the average number of WBS observed was greatest for DADLE (32.8), morphine (30.2) and sufentanil (25.0) while animals treated with DAMGO displayed a significantly less degree of opioid dependence (8.7).
KW - DADLE([D-Ala,D-Leu]enkephalin)
KW - DAMGO ([D-Ala,MePhe,Gly-ol]enkephalin
KW - Intrathecal infusion
KW - Morphine
KW - Opioid dependence
KW - Sufentanil
UR - http://www.scopus.com/inward/record.url?scp=0024333357&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(89)90360-9
DO - 10.1016/0014-2999(89)90360-9
M3 - Article
C2 - 2553435
AN - SCOPUS:0024333357
SN - 0014-2999
VL - 166
SP - 467
EP - 472
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 3
ER -