Increased sensitization to morphine-induced oral stereotypy in aged rats

Abstract

Sensitization develops to the stereotypic biting behavior that appears with the repeated administration of high dose morphine to rats. Because there is evidence that this behavior is dopamine-mediated and that there are age-related changes in dopamine systems, we compared the development and expression of morphine-induced biting behavior in aged (24 months) and young rats (5 months). Animals were treated with four sensitizing 10 mg/kg doses of morphine or saline, followed by three weekly challenges with 4 mg/kg doses of morphine or saline. By the fourth sensitizing morphine dose and after the administration of each low dose challenge, the biting time was significantly greater for aged than for young morphine pre-treated rats. After the first weekly low dose challenge, the aged but not young animals expressed more biting than when they did after the last 10 mg/kg dose. These results indicate that sensitization to morphine-induced oral stereotypy is significantly greater in aged as compared to young rats. Age-related enhanced sensitivity to morphine-induced oral stereotypy might be related to age-induced increases in vulnerability to opioid-induced insults to the basal ganglia, and may be a model for certain diseases of this pathway.