title: Mild stress sensitizes the brain's response to morphine.
abstract: Behavioral experiments demonstrate that stress alters the individual's attitude towards opiates. In search for the underlying neuronal mechanisms we investigated the influence of stress on morphine-induced c-fos expression in the brain, and, vice versa, the influence of morphine application on the brain's c-fos response to stress. In our experiments, mild stress was induced either by brief immobilization (1 min) or by exposing the rats to a noisy and unfamiliar environment. These kinds of stress, unlike severe stress, did not elicit c-fos expression in the paraventricular nucleus of the hypothalamus. However, c-fos expression was observed in the lateral septum, medial striatum, claustrum and in the cingulate and piriform cortices under these conditions. The stress-induced c-fos induction was markedly decreased by a moderate (10 mg/kg) dose of morphine. On the other hand, morphine alone (50 mg/kg) caused only a weak c-fos expression in nai;ve animals despite of the rather high dose. If, however, this morphine dose was applied in the presence of a stressful stimulus, a pronounced c-fos expression in the dorsal striatum resulted. This c-fos signal was comparable with the signal seen in morphine-sensitized animals. Thus, distressing conditions seem to alter the brain's response to morphine at the level of gene expression, and this could be important for initiating voluntary opiate intake.
authors.affiliation: Institute for Pharmacology and Toxicology, Otto von Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Mayer
authors.forename: M
authors.initials: M
authors.lastname: Erdtmann-Vourliotis
authors.forename: U
authors.initials: U
authors.lastname: Riechert
authors.forename: S
authors.initials: S
authors.lastname: Ammon
authors.forename: V
authors.initials: V
authors.lastname: Höllt
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology*; D004780:Environment, Controlled; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009622:Noise / Q000009:adverse effects; D009293:Opioid-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D009020:Morphine