Jodie J. Rady, Jennifer M. Gorny and James M. Fujimoto
Research Service, Clement J. Zablocki Veterans Affairs Medical Center,
Milwaukee, WI 53295, USA
Abstract: CD-1 mice were treated intravenously with streptozotocin,
200 mg/kg, and tested 2 weeks later or treated with 60 mg/kg and tested
3 days later. Both treatments changed the tail flick response of heroin
and 6-monoacetylmorphine (6 MAM) given intracerebroventricularly from a
mu- to delta-opioid receptor-mediated action as determined by differential
effects of opioid receptor antagonists. The response to morphine remained
mu. Heroin and 6 MAM responses involved delta1 (inhibited by
7-benzylidenenaltrexone) and delta2 (inhibited by naltriben)
receptors, respectively. These delta-agonist actions did not synergize with
the mu-agonist action of morphine in the diabetic mice. The expected synergism
between the delta agonist, [D-Pen2-D-Pen5]enkephalin
(DPDPE), and morphine was not obtained in diabetic mice. Thus, diabetes
disrupted the purported mu/delta-coupled response. In nondiabetic CD-1 mice,
heroin and 6 MAM produced a different mu-receptor response (not inhibited
by naloxonazine) from that of morphine (inhibited by naloxonazine). Also,
these mu actions, unlike that of morphine, did not synergize with DPDPE.
The unique receptor actions and changes produced by streptozotocin suggest
that extrinsic in addition to genetic factors influence the opioid receptor
selectivity of heroin and 6 MAM.
Keywords: Streptozotocin, Heroin antinociception, mu- and delta-opioid,
Receptor selectivity change