Maternal care, hippocampal glucocorticoid receptors, and hypothalamic- pituitary-adrenal responses to stress

Science

Volumn 277, Issue 5332, 1997, Pages 1659-1662

  Liu, Dong ^a   Diorio, Josie ^a   Tannenbaum, Beth ^a   Caldji, Christian ^a   Francis, Darlene ^a   Freedman, Alison ^a   Sharma, Shakti ^a   Pearson, Deborah ^a   Plotsky, Paul M ^b   Meaney, Michael J ^a  

^a MCGILL UNIVERSITY   (Canada)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CORTICOSTERONE; CORTICOTROPIN; GLUCOCORTICOID; GLUCOCORTICOID RECEPTOR; MESSENGER RNA;

ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; HIPPOCAMPUS; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; MATERNAL CARE; MOTHER CHILD RELATION; NEUROENDOCRINE SYSTEM; NONHUMAN; PRIORITY JOURNAL; RAT; STRESS;

ADRENOCORTICOTROPIC HORMONE; ANIMALS; ANIMALS, NEWBORN; CORTICOSTERONE; CORTICOTROPIN-RELEASING HORMONE; FEEDBACK; FEMALE; GENE EXPRESSION REGULATION; GROOMING; HANDLING (PSYCHOLOGY); HIPPOCAMPUS; HYPOTHALAMO-HYPOPHYSEAL SYSTEM; MATERNAL BEHAVIOR; PITUITARY-ADRENAL SYSTEM; RATS; RECEPTORS, GLUCOCORTICOID; RNA, MESSENGER; STRESS;

ANIMALIA;

EID: 15144344289     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.277.5332.1659     Document Type: Article

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34. S. Levine and G. W. Lewis, Science 129, 42 (1959); J. Meaney and D. H. Aitken, Dev. Brain Res. 22, 301 (1985). The animals used in all studies were Long-Evans hooded rats obtained from Charles River Labs. (St. Constant, Québec, Canada) and housed in 46 cm by 18 cm by 30 cm Plexiglas cages that permitted a clear view of all activity within the cage. Food and water were provided ad libidum. The colony was maintained on a 12:12 light:dark (L:D) schedule with lights on at 0800. All procedures were done in accordance with guidelines developed by the Canadian Council on Animal Care and protocol approved by the McGill University Animal Care Committee. Handling was done as described (2). Nonhandled animals were completely undisturbed until day 12 of life at which time normal cage maintenance was initiated. The behavior of each dam was observed [M. M. Myers, S. A. Brunelli, H. N. Shair, J. M. Squire, M. A. Hofer, Dev. Psychobiol. 22, 55 (1989)] for eight 60-min observation periods daily for the first 10 days after birth with six periods during the light phase and two periods during the dark phase of the L:D cycle. The distribution of the observations was based on the finding that nursing in rats occurs more frequently during the light phase of the cycle. Handling occurred each day at 1100, and an observation was scheduled at 1130 to correspond to the reunion of the mothers and pups. Within each observation period the behavior of each mother was scored every 4 min (15 observations per period × 8 periods per day = 120 observations per mother per day) for mother off pups, mother licking and grooming any pup, or mother nursing pups in either an arched-back posture, a "blanket" posture in which the mother lies over the pups, or a passive posture in which the mother lies either on her back or side while the pups nurse. Behavioral categories are not mutually exclusive.
35. S. Levine and G. W. Lewis, Science 129, 42 (1959); M. J. Meaney and D. H. Aitken, Dev. Brain Res. 22, 301 (1985). The animals used in all studies were Long-Evans hooded rats obtained from Charles River Labs. (St. Constant, Québec, Canada) and housed in 46 cm by 18 cm by 30 cm Plexiglas cages that permitted a clear view of all activity within the cage. Food and water were provided ad libidum. The colony was maintained on a 12:12 light:dark (L:D) schedule with lights on at 0800. All procedures were done in accordance with guidelines developed by the Canadian Council on Animal Care and protocol approved by the McGill University Animal Care Committee. Handling was done as described (2). Nonhandled animals were completely undisturbed until day 12 of life at which time normal cage maintenance was initiated. The behavior of each dam was observed [M. M. Myers, S. A. Brunelli, H. N. Shair, J. M. Squire, M. A. Hofer, Dev. Psychobiol. 22, 55 (1989)] for eight 60-min observation periods daily for the first 10 days after birth with six periods during the light phase and two periods during the dark phase of the L:D cycle. The distribution of the observations was based on the finding that nursing in rats occurs more frequently during the light phase of the cycle. Handling occurred each day at 1100, and an observation was scheduled at 1130 to correspond to the reunion of the mothers and pups. Within each observation period the behavior of each mother was scored every 4 min (15 observations per period × 8 periods per day = 120 observations per mother per day) for mother off pups, mother licking and grooming any pup, or mother nursing pups in either an arched-back posture, a "blanket" posture in which the mother lies over the pups, or a passive posture in which the mother lies either on her back or side while the pups nurse. Behavioral categories are not mutually exclusive.
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37. D. Liu et al., data not shown.
38. Nine Long-Evans female rats were mated in our animal facility and housed and observed as described (16). The animals underwent routine cage maintenance beginning on day 12 but were otherwise not manipulated. At the time of weaning on day 22 of life, the male offspring were housed in same-sex, same-litter groups. Testing of offspring occurred no earlier than 100 days of age.
39. We then rank-ordered the dams on licking and grooming, identifying those mothers whose scores fell above the mean, and as a group these dams were classified as high LG-ABN. The remaining dams were classified as low LG-ABN. The offspring were tested beginning at 100 days of age.
40. For restraint stress (20 min) testing (6), two animals from each of the nine litters were randomly selected for testing. Blood samples were collected from indwelling right jugular vein catheters (6), implanted 4 days before restraint stress testing, and replaced with an equal volume of normal saline (0.9%) via the same route. We have found that by 72 hours after surgery, basal ACTH and corticosterone levels have returned to normal (6). Plasma corticosterone was measured by radioimmunoassay [L. C. Krey et al., Endocrinology 96, 1088 (1975)].
41. Plasma (25 μl) ACTH was measured by radioimmunoassay as described [C.-D. Walker, S, F. Akana, C. S. Cascio, M. F. Dallman, ibid. 127, 832 (1990);
42. V. Viau and M. J. Meaney, ibid. 129, 2503 (1991)]. All samples were run within a single assay. In our lab the intra- and interassay coefficients of variation are 7 and 10%, respectively, for corticosterone and 8 and 11% for ACTH. The data were analyzed by two-way analyses of variance (ANOVA) with one between (group) and one within (sample) measure. Post hoc analysis was performed by Tukey test.
43. We used a delayed negative-feedback paradigm [M. Keller-Wood and M. F. Dallman, Endocr. Rev. 5, 1 (1984)] in which animals are steroid-treated 2 to 4 hours before acute stress. The animals used in this study were the same animals prepared with jugular catheters for acute restraint testing. The animals were tested 4 days after restraint stress, and all but one of the catheters remained patent during this interval. The critical measure here is the ability of the steroid to inhibit subsequent HPA responses to stress. Animals were injected subcutaneously with either vehicle alone or a low to moderate dose of corticosterone (1 mg/kg in ethanol:saline/1:9) on the basis of earlier studies (6) showing that this dose discriminates feedback sensitivity in handled versus nonhandled rats. Restraint stress was done as described above and plasma samples were obtained from jugular catheters immediately before and at the end of the 20-min period of restraint, a time point that corresponds to the peak plasma ACTH level (6). The percentage suppression of plasma ACTH responses to stress for the high-versus low-LG-ABN groups was derived by comparing Δ(peak stress level - basal level) for each of the corticosterone-treated animals in both groups with that of the mean for the respective control groups (vehicle-treated high-or low-LG-ABN animals). Percentage suppression scores were used to accommodate for the groups differences in plasma ACTH responses to acute stress. The results were examined statistically by Mann-Whitney U test on the basis of percentage scores.
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48. 35S]UTP-labeled cRNA antisense probes transcribed with T 7 RNA polymerase from a 674-bp Pst I-Eco RI fragment of the rat GR cDNA linearized with Ava I. After hybridization, sections were dehydrated, dried, and dipped in photographic emulsion (NTB-2, Kodak), and then stored at 4°C for 21 days before development and counter-staining with Cresyl Violet. The hybridization signal within dorsal hippocampal subregions was quantified by grain counting within high-power microscopic fields under brightfield illumination. Grain counting was performed by an individual unaware of the group from which the slide was derived. For each cell field, grains over ∼40 to 50 individual neurons per section were counted, on three sections per animal (9). After subtraction of background (grains over neuropil), mean values were derived for each hippocampai cell field for each animal. Background ranged between 10 and 15% of values found over hippocampal cells. Grain counts are presented as a function of cell area to account for possible morphological differences [J. T. McCabe, R. A. Desharnais, D. W. Pfaff, Methods Enzymol. 168, 822 (1989)]. These data were analyzed by two-way ANOVA with one between measures (group) and one repeated measure (hippocampal sub-field) by Tukey post hoc test.
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59. We thank R. Meisfield (Univ. of Arizona) for rat GR cDNA and H. Anisman and M. Hofer for comments on an earlier version of this manuscript. Supported by grants from the Medical Research Council of Canada (MRCC) (M.J.M.) and the National Institute of Mental Health (P.M.P. and M.J.M.). M.J.M. is the recipient of an MRCC Scientist award. D.L. is a graduate fellow of the MRCC.