Prenatal ethanol exposure: sex differences in anxiety and anxiolytic response to a 5-HT1A agonist.
ABSTRACT This study utilized a novelty-induced suppression of feeding task to examine anxiety-like behaviour and the anxiolytic effects of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), in rats prenatally exposed to ethanol. Adult offspring from ethanol exposed (E), pair-fed control (PF) and ad libitum-fed control (C) dams were habituated to a novel palatable food for 21 days and measures of baseline feeding obtained. On day 22 (d 22), animals received either 8-OH-DPAT (0.06 mg/kg) or vehicle (0.9% NaCl) and feeding behaviour in the home cage or a novel cage was observed. Factor analyses revealed that feeding behaviour on d 21 (habituation) and d 22 (test day) are reflective of two different affective states, and that the single factor that emerged for novel cage testing on d 22 likely reflects the anxiety evoked by the novel test condition. Analyses of variance on the variables loading significantly onto the factors support the suggestion that the novel environment is anxiogenic for both females and males, and that 8-OH-DPAT acts as an anxiolytic. However, although both females and males showed alterations in behaviours (latency, amount, duration of feeding) reflective of anxiety, 8-OH-DPAT had anxiolytic effects primarily in females. Importantly, prenatal ethanol exposure altered several aspects of behavior in this task. Both E females and males consumed less than their control counterparts on d 21, suggesting a possible delay or deficit in response habituation. During home cage testing on d 22, overall feeding rate was slower in E than in C females, and E males consumed less than PF and C males. In addition, a smaller percentage of E than PF and C females fed in the novel environment, and latency to feed was significantly increased in E compared to control females. These findings indicate that prenatal ethanol exposure results in increased anxiety-like behaviour in adulthood, and that prenatal ethanol-induced hyponeophagia may be, at least in part, mediated by the 5-HT1A receptor. This study is one of the first to demonstrate specific increases in anxiety-like behaviour in animals prenatally exposed to ethanol, and further supports the utility of the novelty-induced suppression of feeding task in assessing anxiety and the effectiveness of anxiolytic agents.
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ABSTRACT: Previous studies provide evidence that fetal ethanol exposure induces hypothalamic-pituitary-adrenal (HPA) and pituitary beta-endorphin (beta-EP) hyperresponsiveness to acute stressors. The present study demonstrates significant effects of in utero ethanol exposure on the parallel response patterns of the HPA axis and the pituitary beta-EP system to repeated exposures to a stressor, restraint stress, and indicates sex differences in response. Together, data from the two experiments indicate that, after repeated restraint exposures, fetal ethanol-exposed (E) males and females both show significantly increased plasma levels of adrenocorticotropin (ACTH), and E males also show significantly increased plasma levels of beta-endorphin-like immunoreactivity (beta-EPLIR), compared with their respective pair-fed and control counterparts. Marginal increases in the corticosterone response of E males and the beta-EPLIR response of E females, compared with their controls, were also observed. In addition, delayed or deficient habituation to restraint stress was observed in the beta-EPLIR response of E males and the ACTH response of E females. These data demonstrate that fetal E-exposed males and females both exhibit hormonal hyperresponsiveness and/or deficits in recovery after repeated exposures to restraint stress, but that the patterns of response may differ depending on the number and duration of restraint exposures, the time course measured, and whether the endpoint measured is corticosterone, ACTH, or beta-EPLIR. In addition, the finding that E and pair-fed animals both differed from their respective controls in certain developmental and hormonal measures suggests that prenatal nutritional factors may play a role in mediating some of the changes that are observed.Alcoholism Clinical and Experimental Research 03/1996; 20(1):122-31. · 3.42 Impact Factor
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ABSTRACT: This laboratory previously demonstrated that chronic maternal ethanol consumption results in a marked deficiency of cortical serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) and of 5-HT uptake sites in the 19- and 35-day-old offspring. In order to determine whether in utero exposure to ethanol similarly affects other components of the serotonergic system we examined the influence of chronic maternal ethanol consumption on cortical, serotonergic 5-HT1 binding sites in developing offspring. Female Sprague-Dawley rats were pair-fed, using control or 6.6% (v/v) ethanol liquid diets on a chronic basis prior to parturition. Serotonergic 5-HT1 sites were measured in synaptosomal membranes from whole cortex and cortical regions from developing offspring. Serotonergic 5-HT1 sites were assessed by measuring the binding of [3H]-5-HT to synaptosomal membranes in the presence and absence of nonradioactive 5-HT. Serotonergic 5-HT2 sites were blocked by including 100 nM spiperone in the assay buffer. The results demonstrated that the 19- and 37-day-old offspring of ethanol-fed rats had a significant (approximately 10-40%) reduction in the Bmax for serotonergic 5-HT1 binding sites on synaptosomal membranes from whole cortex (p less than 0.025), motor cortex (p less than 0.01), and somatosensory cortex (p less than 0.025). However, the binding affinity (Kd) for serotonin was not significantly altered (p greater than 0.05). These results emphasize the sensitivity of the developing cortical serotonergic system to prenatal ethanol exposure.Alcohol 01/1988; 5(6):465-70. · 2.26 Impact Factor
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ABSTRACT: Although numerous behavioral tests are available to assess anxiety, we introduce a simplified version of a previously established test that is exquisitely sensitive and reliable. The latency to consume a palatable snack (graham wafer crumbs) was assessed among mice in their home cage and in an unfamiliar environment, as well as in the presence or absence of predator scent. The effects of various anxiolytics and nonanxiolytics were evaluated in these paradigms. When offered the palatable snack in a familiar environment, mice readily approached and began consumption; however, in a novel environment (cage with fresh bedding), or in the presence of predator scent (rat feces), response latencies increased 10-fold. Anxiolytics, including diazepam, chlordiazepoxide, propranolol, or chronic treatment with either buspirone or the antidepressant desmethylimipramine attenuated the effects in the novel environment without affecting home-cage responding. In contrast, nonanxiolytic agents (haloperidol, amphetamine, acute buspirone or desmethylimipramine) failed to exclusively affect novel environment-induced prolongation of response latencies. The simplicity of design, the absence of food deprivation or neurogenic stressors, the possibility of using it in a repeated measures design, the reliability and magnitude of response, and the specificity and sensitivity to anxiolytic drugs makes this an ideal preparation with which to assess anxiety and anxiety-altering manipulations.Biological Psychiatry 10/2003; 54(5):552-65. · 9.25 Impact Factor