title: Early neonatal experience of Long-Evans rats results in long-lasting changes in reactivity to a novel environment and morphine-induced sensitization and tolerance.
abstract: In Long-Evans rats, daily 3-h separation from the dam during the neonatal period results in enduring alterations in behavioral and neuroendocrine responses to stressors and sensitivity to antinociceptive effects of acute and chronic morphine. We tested whether early neonatal experience alters sensitivity to effects of morphine on locomotor activity. The subjects were adult rats that had one of the following backgrounds: daily separation from the dam on postnatal days 2-14 for either 3 h (maternal separation (MS)) or 15 min (handled control (H)) or no separation from the dam (non-handled control (NH)). After two consecutive days of baseline activity measurements, subjects were tested daily after SC injections of either morphine (10 mg/kg) or saline for seven days and again on day 10. Beginning five days later, saline and 1.0-10 mg/kg of morphine were tested in all animals. On the baseline days, MS animals had higher horizontal and vertical activity than did NH controls, whereas H animals spent more time in the center of the testing chamber. In MS and H animals but not in NH controls, daily injections of morphine produced progressive increases in all locomotor activity measures, indicative of sensitization (horizontal counts, center time) and tolerance (vertical counts). MS animals with a history of morphine treatment had significantly higher horizontal and vertical activity after a saline injection than did their counterparts with a history of saline treatment, indicative of conditioning. They also exhibited greater locomotor sensitization to 1.0 mg/kg of morphine than did H and NH controls. These results provide further evidence that environmental manipulation in the form of maternal separation early in life results in enduring changes in sensitivity to effects of morphine that could reflect altered endogenous opioid systems.
authors.affiliation: Department of Pharmacology, Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Suite 5074, Atlanta, GA 30322, USA. mkalini@emory.edu
authors.forename: Mikhail
authors.initials: M
authors.lastname: Kalinichev
authors.forename: Keith W
authors.initials: KW
authors.lastname: Easterling
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Holtzman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004361:Drug Tolerance / Q000502:physiology*; D004780:Environment, Controlled; D006234:Handling, Psychological; D008297:Male; D008426:Maternal Deprivation; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D018847:Opioid Peptides / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011957:Receptors, Opioid / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology; D019966:Substance-Related Disorders / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D018847:Opioid Peptides; D011957:Receptors, Opioid; D009020:Morphine