Rationale: Vulnerability for development of substance abuse is often associated with a "sensation-seeking" or "thrill-seeking" phenotype. In an animal model, rats more reactive in a novel environment (high responders, HR) are more sensitive to stimulant/reinforcing effects of amphetamine and are more likely to self-administer this drug, than are less reactive animals (low responders, LR).
Objective: We tested whether HR and LR also differ in sensitivity to effects of morphine on locomotor activity.
Methods: Male Sprague-Dawley rats were categorized as HR or LR based on motor responses to novelty (sorting day; S). After 1 day (B) of baseline activity measurements, subjects were tested daily after SC injections of either morphine (10 mg/kg) or saline for 7 days and again on day 10. Beginning 5 days later, four daily injections of saline and 1.0-10 mg/kg morphine were tested in all animals.
Results: LR and HR were similar in the onset and overall magnitude of sensitization and tolerance following daily morphine administration. HR were more sensitive than LR to locomotor stimulant effects of acute morphine. However, LR had more robust and persistent context-specific increases in activity due to conditioning than did HR, and expression of sensitization was apparent in all behavioral variables.
Conclusions: These results provide further evidence that phenotypic differences between HR and LR may, in part, be associated with differences in the endogenous opioid systems. Differences in sensitivity to acute versus repeated morphine suggest that at least in relation to opioid drugs, these phenotypes may reflect different aspects of drug vulnerability rather than simply the presence or absence of it.