Enhanced development of morphine tolerance in rats treated with 2-deoxy-d-galactose

Rats treated subcutaneously for 6 days with morphine developed a weak tolerance which was characterized by a decrease in the analgesic action of the opioid. Under those experimental conditions a simultaneous intracerebroventricular application of 2-deoxy-d-galactose enhanced development of morphine tolerance, while other deoxy-sugars like 2-deoxy-d-glucose and 6-deoxy-d-galactose were ineffective. In contrast, no influence of 2-deoxy-d-galactose on a more enhanced morphine tolerance after a 11-day pretreatment with morphine was found. The results are discussed in the light of a rather specific interference of 2-deoxy-d-galactose with neuronal glycoprotein processing and related cellular mechanism underlying adaptive processes involved in the development of morphine tolerance.