Effects of the intravenous administration of [Lys7]dermorphin on local cerebral glucose utilization in the rat

The use of analgesic opioids in the clinical setting is hampered by the reinforcing and addictive properties of these drugs. Moreover, chronic administration of conventional opioids is accompanied by progressive reduction of the analgesic effects, that often forces clinicians to increase dosages, exposing a subject to serious side-effects. Thus, interest is growing in the development and characterization of synthetic opioid agonists with lower reinforcing properties than conventional opioids. [Lys7]dermorphin is a μ1 receptor agonist with 20-30 times stronger analgesic properties than morphine. Previous data indicate that the drug causes fewer side-effects than conventional opioids, and is less likely to produce physical dependence than morphine. In this study we investigated the effects of the intravenous administration of a range of doses of [Lys7]dermorphin (0.002, 0.01 and 0.05 mg/kg) on local cerebral glucose utilization in the rat, by means of the quantitative [14C]2-deoxyglucose method. The results of the study showed dose-related reductions of cerebral metabolic rates for glucose in limbic, sensory-motor and autonomic regions following the intravenous administration of [Lys7]dermorphin. Such pattern of changes is similar to those measured earlier following the administration of analgesic doses of drugs stimulating μ-opioid receptors. Within the nucleus accumbens, and the shell portion in particular, we did not measure any increase of glucose utilization, rather a significant decrease following the administration of the higher dose of [Lys7]dermorphin. These findings contribute to the definition of the functional consequences of the administration of [Lys7]dermorphin, and indirectly suggest the lack of effect of the drug on mesolimbic dopamine neurotransmission.