The maternal consumption of alcohol during pregnancy produces a wide range of
abnormalities in the offspring. The major objectives of this thesis were to investigate (1) the
correspondence between prenatal ethanol-induced alterations in behavior and in hypothalamicpituitary-
adrenal (HPA) activity, (2) the ability of early postnatal handling as an environmental
manipulation to attenuate at least some of the adverse behavioral and physiological consequences
of prenatal ethanol exposure, and (3) possible mechanisms mediating the HP A
hyperresponsiveness to stressors observed in animals prenatally exposed to ethanol and the
possible influence of postnatal handling on those mechanisms. Sprague-Dawley rats from
prenatal ethanol (E), pair-fed (PF) and ad libitum fed control (C) treatment groups were tested as
young adults (-35-120 d of age) or mid-aged adults (13-14 months of age).
The first study investigated the effects of prenatal ethanol exposure (E) and postnatal
handling (H) on behavior and HPA activity during a conditioned taste aversion (CTA) task.
We tested the hypothesis that E animals which underwent postnatal handling would show
improved conditioned aversion learning and reduced HPA activity compared to E animals
that did not experience handling (nonhandled, NH). We found that prenatal ethanol exposure
and postnatal handling independently resulted in an increased rate of consumption of a saccharin
solution over five preexposure days. In addition, we found that handling differentially affected
posttoxicosis consumption of the conditioned solution as well as corticosterone (CORT) levels in
E, PF and C animals. H-E animals showed increased posttoxicosis intake compared to H-PF and
H-C animals during reexposure under non-deprived conditions; CORT levels were lower in PF
and C than E males compared to their N H counterparts during reexposure under food- and waterdeprived
conditions. Thus, E animals were less able to utilize environmental cues in the present
study, displaying a more rapid reduction in neophobia compared to PF and C animals and,
following postnatal handling, showing a decreased acquisition of conditioned aversion and an
increased CORT response during reexposure to the conditioned solution.
The second study examined spatial learning and memory in young adult (2 months)
and mid-aged (13-14 months of age) H and N H E and control animals utilizing a Morris
water maze. We investigated the hypothesis that postnatal handling would improve spatial
navigation in E animals compared to E animals that did not experience handling and/or attenuate
differences among E and control animals, and that this effect might be age-dependent. We also
examined whether performance deficits in mid-aged animals would correspond to increases in
CORT levels on the last day of testing. Young E males showed impairments in spatial
navigation compared to young PF and C animals, taking longer to find the hidden platform over
the course of testing and displaying an alteration in search pattern when the platform was
removed. Interestingly, differences in young E, PF and C animals in escape latency and in
distance traveled prior to finding the platform were apparent in H but not in N H animals. There
were no differences in performance on the Morris water maze in mid-aged E, PF and C animals,
but CORT levels were elevated in mid-aged E compared to C animals, supporting previous data
indicating that E animals demonstrate HPA hyperresponsiveness to stressors. Lastly, although
mid-aged animals had longer escape latencies and an altered search pattern compared to young
animals, handling did not appear to attenuate impairments associated with aging.
The third study investigated the hypothesis that postnatal handling might attenuate
stress-induced ACTH and/or CORT differences among E, PF and C animals. Furthermore,
the ability pf postnatal handling to modulate HPA feedback deficits in E animals was
examined during exposure to a restraint stressor following dexamethasone (DEX)
administration. Both E females and males showed increased ACTH and CORT compared to PF
and/or C animals following saline administration. Administration of DEX to block HPA activity
significantly suppressed both plasma ACTH and CORT in all animals. However, E females
exhibited increased and/or prolonged elevations in ACTH and CORT compared to PF and C
animals following DEX blockade. These data suggest that the insult of prenatal ethanol exposure
affects both male and female offspring, but that there may be a sex-specific difference in
sensitivity of the mechanism(s) underlying HPA hyperresponsiveness. Postnatal handling
reduced ACTH levels in both females and males following saline administration. Following
DEX administration, H males had lower CORT than NH males. Postnatal handling resulted in a
more rapid decrease in stress-associated CORT elevations in C females, and attenuated
differences in CORT between PF and C females. However, postnatal handling did not attenuate
deficits in negative feedback inhibition in E females; E females in both the H and N H treatments
showed elevated CORT compared to their C counterparts, and H-E females also showed elevated
CORT compared to H-PF females. Thus, postnatal handling did not attenuate the typical HPA
hyperresponsiveness to stressors observed in E animals (saline condition), nor did it eliminate
deficits in HPA feedback inhibition in E females (DEX condition).
The fourth study examined whether the mechanisms resulting in HPA
hyperresponsiveness in E animals are similar to those underlying the effects of postnatal
handling. Differences in HPA responsiveness between H and NH animals appear to be
dependent upon basal CORT activity and not stress-induced elevations in CORT. Therefore, we
tested the hypothesis that differences in HPA activity among E and control animals would not
occur following adrenalectomy (ADX) but could be reestablished following replacement with
basal levels of exogenous CORT. In the absence of a CORT feedback signal or in the presence
of a constant, basal CORT feedback signal, E, PF and C animals did not significantly differ in
their abilities to regulate ACTH secretion, indicating that during the trough of the circadian
rhythm, E, PF and C animals are equally capable of regulating HPA activity utilizing either
CORT-independent feedback or feedback mediated through basal CORT activity. Thus, the
effects of prenatal ethanol exposure on HPA function do not appear to be dependent upon the
feedback signal provided by basal CORT levels.
In conclusion, handling did not attenuate the effects of prenatal ethanol exposure
examined in the present experiments. This may be because the effects of postnatal handling and
prenatal ethanol exposure on HPA function are mediated through different mechanisms as well
as the finding that handling is, at least partly, mediated through mother-pup interactions.
Therefore, postnatal handling might exert differential effects on litters in which pup behavior has
already been altered by prenatal treatments, underscoring the enduring effects of prenatal ethanol
exposure.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:BVAU.2429/11143 |
| Date | 11 1900 |
| Creators | Gabriel, Kara Irene |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Relation | UBC Retrospective Theses Digitization Project [http://www.library.ubc.ca/archives/retro_theses/] |
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