There is evidence that older patients require less morphine for effective analgesic relief than younger patients, suggesting that analgesic potency increases with age. At the same time opiate use in addict populations appear to decline as a function of age, suggesting that the hedonic potency of opiates may decrease with age. The proposed experiments will determine if there are differences in the hedonic effects of morphine, the prototypic opiate, as measured by morphine's effect on the threshold for rewarding electrical intracranial stimulation in young, middle-aged and aged rats. These results will be compared to changes in the analgesic response to morphine as determined by threshold changes in escape from aversive electrical brain stimulation in the three age groups of rats. Because rats quickly become sensitized to morphine-induced stereotypic biting and locomotor behavior and this sensitization may be modeling brain changes associated with relapse in the opiate addict; the development and expression of morphine sensitized behavior will be compared in the three group of subjects. Also, because aging may alter patterns of drug distribution and elimination rates, the pharmacokinetics of morphine will be compared in these different aged groups. To our knowledge, the proposed experiments will be the first to examine the relationship between the analgesic and hedonic effects of opiates and aging. The findings of this study may have implications with regard to both pain management and opiate abuse in the elderly.
| Crosby, Steven J; Knapp, Clifford M; Kornetsky, Conan (2006) Nociceptive threshold and analgesic response to morphine in aged and young adult rats as determined by thermal radiation and intracerebral electrical stimulation. Pharmacol Biochem Behav 84:148-57 |
| Jha, Shivkumar H; Knapp, Clifford M; Kornetsky, Conan (2004) Effects of morphine on brain-stimulation reward thresholds in young and aged rats. Pharmacol Biochem Behav 79:483-90 |
| Knapp, Clifford M; Jha, Shivkumar H; Kornetsky, Conan (2004) Increased sensitization to morphine-induced oral stereotypy in aged rats. Pharmacol Biochem Behav 79:491-7 |
