Individual differences in locomotor reactivity to a novel environment and sensitivity to opioid drugs in the rat. I. Expression of morphine-induced locomotor sensitization.
BACKGROUND
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.
Department of Pharmacology, Rollins Research Center, Emory University School of Medicine, 1510 Clifton Road, Suite 5074, Atlanta, GA 30322, USA. mikhail.m.kalinichev@gsk.com
Mikhail
M
Kalinichev
David A
DA
White
Stephen G
SG
Holtzman
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004777:Environment; D007206:Individuality; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D009020:Morphine