[Abstract Title]. - Society for Neuroscience

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 270.20/HH19
Topic: D.08.r. Opioids and other analgesics
Support: NIDA Grant DA 19959 (to B.C.Y)
Title: Effect of dosing protocol on morphine tolerance
Authors: *S. V. DIGHE, S. SIROHI, P. MADIA, B. C. YOBURN;
Col. of Pharm., St. John's Univ., Jamaica, NY
Abstract: Dosing protocol has been proposed to be an important determinant of the magnitude
of opioid tolerance. The present study examined the effect of acute, intermittent and continuous
treatment with morphine on analgesic tolerance. Mice were implanted s.c. with one or two 25mg,
or one 75mg morphine pellet for 7 days. Other mice were injected with morphine once (18.5-
185mg/kg/day; ≈ 10-100 times ED50 for morphine analgesia) or once/day for 7 days. Controls
were implanted with a placebo pellet or injected with saline. Preliminary analysis of drug release
from morphine pellets indicated that a single 25mg pellet released 15.3±0.6mg morphine in
7days (≈ 67mg/kg/day; ≈36 times the ED50 for morphine analgesia) and the 75mg pellet released
23.9±0.9mg in 7days (≈ 123mg/kg/day; ≈66 times the ED50 for morphine analgesia). Pellets were
removed and 16 hr following the end of implantation, or 24 hr following the last injection,
morphine cumulative dose-response studies were conducted (tail flick). Continuous treatment
with morphine using pellet implantation produced a dose-dependent shift in the morphine ED50
by 3.4, 5.2 and 6.7 for one 25mg pellet, one 75mg pellet and two 25 mg pellets, respectively.
Intermittent and acute treatment produced minimal tolerance compared to continuous treatment.
The maximum shift in the ED50 was 1.6 for acute treatment and 2.7 for 7 day intermittent
treatment, despite the larger total dose. The present results indicate that continuous treatment
with morphine (i.e., pellets) results in greater development of analgesic tolerance than acute or
intermittent treatment. These results are consistent with the suggestion that intermittent dosing
has reduced risk of producing opioid tolerance.
Disclosures: S.V. Dighe, None; S. Sirohi, None; P. Madia, None; B.C. Yoburn, None.
Poster
271. Mechanoreceptors
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 271.1/HH20