Paradoxical Effects of Chronic Morphine Treatment on the Temperature and Pituitary-Adrenal Responses to Acute Restraint Stress: A Chronic Stress Paradigm

Body temperature and pituitary-adrenal responses to restraint (15 min or 4 h) stress were evaluated in nondependent and morphine-dependent rats. Male Sprague-Dawley rats were treated twice daily with increasing doses of morphine (10-100 mg/kg, s.c.) for 16 days. Transmitters were implanted in the peritoneal cavity to monitor body temperature and blood was collected for hormone assays. Acute withdrawal from chronic morphine treatment was associated with reduced body weight, increased adrenal weight and decreased thymus weight. Sixteen days after termination of chronic morphine treatment, rats had recovered normal adrenal size, but still displayed marked thymus involution and reduced body weight. Restraint-induced hyperthermia was attenuated in morphine-dependent rats that had undergone 12-h withdrawal. Sixteen days after withdrawal, rats still had not fully recovered the hyperthermic response to restraint. Chronic morphine treatment resulted in a marked elevation of basal corticosterone concentrations. Despite the negative-feedback effects of elevated basal corticosterone concentrations, morphine-dependent rats that had undergone 12-h withdrawal displayed a potentiated and prolonged corticosterone response to restraint stress. In contrast, rats that had undergone 8-day and 16-day morphine withdrawal had recovered normal basal pituitary-adrenal activity, but displayed significantly reduced and shorter adrenocorticotropic hormone and corticosterone responses to restraint. These results suggest that chronic morphine dependence is a chronic stressor, resulting in profound and long-lasting changes in the temperature and pituitary-adrenal responses to acute restraint stress in a time-dependent manner. This morphine-dependence model may be useful in understanding the role that hormonal stress responses play in the maintenance and relapse to opioid use in humans.     

幼年感染细菌内毒素对成年实验性自身免疫性脑脊髓炎大鼠行为和病理的影响

目的：探讨大鼠幼年时期感染细菌内毒素对其成年后实验性自身免疫性脑脊髓炎（EAE）神经功能损伤和中枢神经系统病理学的影响。方法：取同窝SD幼鼠,于出生后第3和第5天2次给予腹腔注射0．01mg·mL^-1脂多糖（LPS）0．05mL或同等剂量无菌生理盐水。成年后（出生后第8周）用豚鼠脊髓匀浆免疫SD大鼠制作EAE模型,观察并比较这两组大鼠行为学与组织病理学变化。结果：与生理盐水对照组相比,LPS处理组SD大鼠EAE发病率明显降低（P〈0．01）,且中枢神经系统内炎症细胞浸润及神经髓鞘脱失也明显减轻（P〈0．01）。结论：幼年时期感染细菌内毒素对成年SD大鼠EAE有明显的保护作用。     

Serotoninergic and Suprachiasmatic Nucleus Involvement in the Corticotropic Response to Systemic Endotoxin Challenge in Rats

We have investigated whether the serotonin system participates in the mechanisms underlying the corticotropic response in experimentally infected rats. Intra-arterial injection of lipopolysaccharide (LPS; 25 microg/kg b.w.) resulted in a slight but significant increase in serotonin (5-HT) metabolism, detectable 60 min after the stimulus and lasting more than 480 min. Adrenocorticotropin (ACTH) and corticosterone (CORT) responses in intact rats conformed to earlier reports, increasing as early as 30 min after LPS injection and reaching maximal concentrations in the circulation 60 min after the bacterial endotoxin injection. Plasma concentrations of interleukin-1beta (IL-1beta) increased only after 60 min, reaching maximal levels 120 min after LPS. Depletion of hypothalamic 5-HT (-93%) by pretreatment of the animals with para-chlorophenylalanine (p-CPA), resulted in a halved ACTH response to LPS, despite an overall unchanged secretory pattern. Neither CORT nor IL-1beta secretory patterns were affected in these rats pretreated with p-CPA. Complete bilateral electrochemical lesions of the suprachiasmatic nucleus (SCN), which is innervated by mesencephalic 5-HT, impaired the early phase of the ACTH (-75% at 30 min) and CORT (-40% at 30 min) responses but did not affect the later increases of the corticotropic and the plasma IL-1beta responses following the LPS injection. These results indicate that serotonin pathways and SCN are involved in the earlier mechanisms of corticotropic axis recruitment following systemic LPS endotoxemia.     

Prenatal Social Stress in the Rat Programmes Neuroendocrine and Behavioural Responses to Stress in the Adult Offspring: Sex‐Specific Effects

Stress exposure during pregnancy can ‘programme’ adult behaviour and hypothalamic‐pituitary‐adrenal (HPA) axis stress responsiveness. In the present study, we utilised an ethologically relevant social stressor to model the type of stress that pregnant women may experience. We investigated the effects of social defeat by a resident lactating rat over 5 days during the last week of pregnancy on the pregnant intruder rat HPA axis, and on HPA responsivity to stress and anxiety‐related behaviour in the adult offspring of the socially‐defeated intruder rats. HPA axis responses after social defeat were attenuated in the pregnant rats compared to virgin females. In the adult offspring, systemic interleukin (IL)‐1β or restraint increased adrenocorticotrophic hormone and corticosterone secretion in male and female control rats; however, in prenatally stressed (PNS) offspring, HPA responses were greatly enhanced and peak hormone responses to IL‐1β were greater in females versus males. Male PNS rats displayed increased anxiety behaviour on the elevated plus maze; however, despite marked changes in anxiety behaviour across the oestrous cycle, there were no differences between female control and PNS rats. Investigation of possible mechanisms showed mineralocorticoid mRNA levels were reduced in the hippocampus of male and female PNS offspring, whereas glucocorticoid receptor mRNA expression was modestly reduced in the CA2 hippocampal subfield in female PNS rats only. Corticotropin‐releasing hormone mRNA and glucocorticoid receptor mRNA expression in the central amygdala was greater in PNS males and females compared to controls. The data obtained in the present study indicate that prenatal social stress differentially programmes anxiety behaviour and HPA axis responses to stress in male and female offspring. Attenuated glucocorticoid feedback mechanisms in the limbic system may underlie HPA axis hyper‐reactivity to stress in PNS offspring.     

Urocortin III, a brain neuropeptide of the corticotropin-releasing hormone family: modulation by stress and attenuation of some anxiety-like behaviours

Following its discovery 20 years ago, corticotropin-releasing hormone (CRH) has been postulated to mediate both hormonal and behavioural responses to stressors. Here, we characterize and describe a behavioural role for the murine gene, UcnIII, which encodes a recently discovered CRH-related neuropeptide, urocortin III. We found that mouse UcnIII is expressed predominantly in regions of the brain known to be involved in stress-related behaviours, and its expression in the hypothalamus increases following restraint. In addition, we found that intracerebroventricular administration of mUcnIII stimulates behaviours that are associated with reduced anxiety, including exploration of an open field and decreased latency to enter the lit compartment of a dark-light chamber, but has no effect on the elevated-plus maze. Finally, we found that mUcnIII does not exert any effects on the hormonal stress response. Based upon our findings, UcnIII may be an endogenous brain neuropeptide that is modulated by stress and stimulates behaviours associated with reduced anxiety. In this capacity, UcnIII may attenuate stress-related behaviours, which may be useful both to help cope with stressful situations as well as to avoid pathology associated with excessive reaction to stressors.     

脂多糖对大鼠黑质纹状体多巴胺能系统的影响

目的　观察脂多糖(lipopolysaccharide , LPS)对大鼠黑质纹状体系统的神经毒性作用,探讨帕金森病(Parkinson disease,PD)与炎症反应的关系。方法　采用立体定向术向大鼠脑黑质注射5μg LPS,于注射后不同时间点(1、3、7、14、21、30 d)观察经腹腔注射阿朴吗啡后大鼠的旋转行为以及采用高效液相色谱(HPLC)测定黑质 纹状体单胺类递质含量的变化;通过免疫组化观察多巴胺(dopamine,DA)合成限速酶酪氨酸羟化酶(tyro sine hydroxylase,TH)的变化。结果　LPS注射后 14、21、30 d大鼠出现向注射侧的旋转行为,黑质 纹状体 DA及其代谢产物随时间延长呈不同程度下降(P<0 05),而 5 羟色胺(5 HT)仅有短暂下降,去甲肾上腺素(nora drenaline,NA)无变化。TH阳性细胞数在第3天开始下降为对照组的45%,14 d时为对照组的5%~10%,30 d时几乎完全消失。结论　LPS注射黑质后能特异性损害DA能神经元,可用于建立PD免疫炎症动物模型。     

Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults

Catecholamine-containing projections from the medulla have been implicated in the mediation of activational responses of the paraventricular nucleus of the hypothalamus (PVH) provoked by moderate doses of interleukin-1 (IL-1). To test the generality of this mechanism, rats bearing unilateral transections of aminergic projections were challenged with intravenous IL-1 (2 microg/kg), bacterial lipopolysaccharide (LPS; 0.1, 2.0, or 100 microg/kg), or saline and perfused 3 hours later; their brains were then prepared for quantitative analysis of Fos induction and relative levels of corticotropin-releasing factor (CRF) mRNA. LPS provoked a robust and dose-related increase in Fos expression within the PVH on the intact side of the brain at all doses tested; the response to IL-1 approximated that to the lowest LPS dose. On the lesioned side, Fos induction was significantly reduced at all dosage levels but was eliminated only at the lowest dosage. The percentage reduction was greatest (75%) in IL-1-challenged rats and was progressively less in animals treated with increasing LPS doses (67, 59, and 46%, respectively). Specificity of aminergic involvement was tested by using intra-PVH administration of the axonally transported catecholamine immunotoxin, antiDBH-saporin. This treatment abolished IL-1-induced elevations of Fos-ir and CRF mRNA in the PVH but left intact comparable responses to restraint stress. These data support a specific involvement of ascending catecholaminergic projections in mediating PVH responses to IL-1 and LPS. Residual Fos induction seen in lesioned animals in response to higher doses of LPS provides a basis for probing additional circuits that may be recruited in a hierarchical manner in response to more strenuous or complex immune insults.     

The Effects of Centrally Administered Porcine Relaxin on Drinking Behaviour in Male and Female Rats

Of the reproductive hormones it has been suggested that relaxin may play an important role in the increased sodium appetite of pregnancy. ICV injection of porcine relaxin caused water-replete male and female Wistar rats with access to water and 0.9% or 2.7% NaCl to drink on average about 3 to 8 ml of water within 1 h of injection. By 24 h the cumulative intake of water was no different from the control intake. The amounts of water drunk were similar after doses of 50, 100, 250 and 500 ng of relaxin. A dose of 5 ng was ineffective. Male rats generally drank more water than female rats after ICV injection of angiotensin or relaxin. Male SH rats which drink more water than male WKY rats in response to ICV angiotensin also drank more after ICV relaxin. Intakes of 0.9% or 2.7% NaCl were unaffected for up to 24 h after injection of relaxin, whereas angiotensin-injected rats showed a significant increase in 0.9% NaCl 1 h after injection though this difference was no longer evident in the 24 h cumulative intake. Relaxin did not cause any increase in NaCl intake in SH rats. Insulin, which is similar in structure and molecular weight to relaxin, was without effect on drinking when doses comparable to dipsogenically effective doses of relaxin were injected ICV. In male Wistar rats treated with DOCA for 5–15 days, relaxin retained its weak stimulatory action on water intake but did not affect NaCl intake despite the increased baseline NaCl intake during DOCA. These results indicate that relaxin is a dipsogen in the rat but that it seems to have little short-term effect on sodium appetite.     

The Ultradian and Circadian Rhythms of Free Corticosterone in the Brain are Not Affected by Gender: An In Vivo Microdialysis Study in Wistar Rats

Recently, we described that free corticosterone levels in the brain of male Wistar rats, as assessed by in vivo microdialysis, show an ultradian rhythm with a pulse frequency of 1.2 pulses/h. To establish whether gender influences brain free corticosterone rhythms, we studied free corticosterone levels in the female Wistar rat under baseline and stressful conditions using microdialysis in the hippocampus. Analysis of the data with the PULSAR algorithm revealed that hippocampal free corticosterone levels show a clear ultradian pattern in female rats with a pulse frequency of 1.16 ± 0.05 pulses/h between 09.00 h and 21.00 h. Further analysis showed that the pulse amplitude is significantly higher during the late afternoon/early night (15.00–21.00 h) than during the morning/early afternoon (09.00–15.00 h) phase (0.13 ± 0.03 versus 0.07 ± 0.01 μg/dl, respectively, P < 0.05). Pulse characteristics were extremely reproducible as demonstrated by the almost identical pulse parameters derived from two consecutive 24‐h periods [pulse frequency: 1.13 ± 0.09 and 1.19 ± 0.08 pulses/h; pulse amplitude: 0.11 ± 0.05 and 0.10 ± 0.02 μg/dl for day 1 and day 2 (09.00–21.00 h) respectively, P > 0.05]. Both exposure to a novel environment and forced swim stress increased hippocampal free corticosterone levels. However, the stress‐induced rise reached higher levels and was more prolonged after forced swimming (area under the curve: 46.84 ± 9.25 and 12.08 ± 1.69 arbitrary units for forced swimming and novelty stress respectively, P = 0.01). Importantly, the ultradian rhythm was rapidly restored after termination of the stress response. This is the first demonstration that the female rat brain is exposed to free corticosterone levels that follow a circadian as well as an ultradian pattern and show almost identical pulse characteristics as recently reported in male animals. These observations are of significance for further investigations into the dynamics of glucocorticoid action in the brain of both genders.     

Neurotrophic Effects of Testosterone on the Medial Nucleus of the Amygdala in Adult Male Rats

Our previous reports of major sex differences in the substance P-immunoreactive (SPir) innervation of the medial posterior divisions of the bed nucleus of the stria terminalis (BST) and medial nucleus of the amygdala in rats raised the question of the hormonal regulation of this innervation. We now report the results of two experiments which examined the effects of castration of adult males on the SPir innervation of these regions. In experiment 2 we asked whether castration might also alter the cytoarchitecture of these regions. In experiment 1 three groups; sham operated (Sham), castrated (C) and castrated plus testosterone (C + T) were examined at each of the three survival periods (2, 4 and 8 weeks) post castration. Animals of the C + T groups each received a 45 mm silastic implant of testosterone sc at the time of castration to maintain testosterone levels postoperatively. Castration produced a consistent and highly significant decrease in the area of dense SPir fiber staining in the posterior medial amygdala which became greater with increasing survival. By 8 weeks the area of staining was 42% smaller in group C as compared to the matched sham-operated group. Smaller decreases were seen in the size of the dense field of SPir fibers in the posterior part of the dorsomedial BST. Testosterone implants maintained the size of the SPir fields of fibers in both the medial amygdala and BST, as the areas of staining in the C + T groups were not significantly different from those in the Sham groups at any of the 3 survival times. In experiment 2 we measured the area and optical density of SPir fiber staining in the medial amygdala and medial BST at 8 weeks post-castration. In addition, we measured the size of the cell groups within these regions using cresyl-stained sections. As in experiment 1, at 8 wks following castration there was a marked decrease in the area of dense SPir staining in both the BST and medial amygdala. The sizes of the dense fields of fibers were reduced by approximately 23% in the BST and by 40% in the posterior medial amygdala. Castration also significantly reduced the optical density of staining within the medial amygdala. The major finding of experiment 2 is that castration affects the cytoarchitecture as well as the SPir staining in these areas. In the BST, the cell group BSTMPM receives most of the dense SPir innervation. Gonadectomy reduced the size of BSTMPM by approximately 28%. In the amygdala, the cell group MePD receives most of the dense SPir innervation. Gonadectomy reduced the size of MePD by approximately 27%, while its neighbour MePV was reduced by a similar degree (26%). These atrophic changes are at least somewhat specific, as other features such as brain weight, the overall size of the forebrain as estimated from whole coronal sections, and the size of the suprachiasmatic nucleus were unchanged. The atrophic changes in the cytoarchitecture of the posterior medial amygdala and BST suggest that the changes in SPir staining seen in experiments 1 and 2 may be secondary to structural atrophy, including reduced axonal and dendritic branching, of hormone responsive SP-containing neurons. The time course of the response to castration demonstrated in experiment 1 suggests that these changes in SP-containing neurons are relevant to the gradual decline in male sexual behavior which follows castration.     

Effects of halothane and methoxyflurane on the hypothalamic-pituitary-adrenal axis in rat

Effects of acute exposure (2 h) to either 1.5% halothane or 0.5% methoxyflurane on chemical mediators of the hypothalamic-pituitary-adrenal (HPA) axis were evaluated in male Sprague–Dawley rats immediately after exposure, after the righting reflex (4 h), or 24 h postexposure. Effects of these anesthetics on hippocampal corticotropin releasing factor (CRF) were also evaluated.Methoxyflurane caused significant elevations in pituitary adrenocorticotropin hormone (ACTH)-like immunoreactivities in all three of the experiment’s time groups, yet halothane failed to cause the same response immediately after exposure. Serum ACTH-like immunoreactivities were significantly elevated immediately after exposure to both anesthetics, but were not elevated at 4 and 24 h postexposure. Corticosterone (CORT)-like immunoreactivities were significantly elevated by halothane in all experimental groups, and in the 2- and 24-h groups following methoxyflurane exposure. Hippocampal CRF-like immunoreactivities remained unaffected by either anesthetic.Results indicate that a 2-h exposure to either halothane or methoxyflurane results in significant activation of the rat hypothalamic-pituitary-adrenal axis, and that the activation appears to be sustained over a 24-h period.     

Preoptic Unit Responses to Microelectrophoresis of Neurotensin and its Antiserum in Female Rats

We and other investigators have demonstrated the stimulation of luteinizing hormone secretion following the microinjection of neurotensin (NT) into the medial preoptic area in female rats. The present study electrophysiologically examined the action of the peptide in the same brain region. Microelectrophoresis of NT produced either excitation or inhibition in 24% of the medial preoptic neurons tested in oestrogen-primed and unprimed ovariectomized animals. Effective blockade of NT-induced excitatory and inhibitor unit responses by means of the simultaneous application of an antiserum to NT (anti-NT) indicated that they were produced by specific actions of the peptide. In addition, anti-NT by itself altered the spontaneous firing rate in some NT-responsive cells. These findings are in accord with the hypothesis that the preoptic area is a site of the action of NT in the female rat.     

The Central Effects of Orexin-A in the Hypothalamic-Pituitary-Adrenal Axis In Vivo and In Vitro in Male Rats

Orexin-A is synthesized in the posterolateral hypothalamus and immunoreactive fibres project to many central nervous system structures, including the paraventricular nucleus, which is rich in corticotropin releasing factor (CRF) neurones and neuropeptide Y (NPY) innervation. We investigated the central effects of orexin-A on the hypothalamic-pituitary-adrenal (HPA) axis by measuring plasma concentrations of corticosterone and adrenocorticotropic hormone (ACTH) in vivo. We explored the potential neuropeptide pathways involved by investigating the effects of orexin-A on CRF, NPY, arginine vasopressin (AVP) and noradrenaline release from hypothalamic explants in vitro. Intracerebroventricular (i.c.v.) injection of orexin-A (3 nmol) in male rats stimulated increases in plasma concentrations of corticosterone between 10 and 40 min after injection, and of plasma ACTH at 20 and 90 min after injection. Orexin-A significantly stimulated CRF and NPY release from hypothalamic explants in vitro. Orexin-A did not stimulate CRF release in the presence of the selective NPY Y1 receptor antagonist, BIBP3226. BIBP3226 alone did not alter CRF release from hypothalamic explants. Orexin-A had no effect in vitro on the release of other neuropeptides, AVP and noradrenaline, involved in the central regulation of the HPA axis. These results suggest that orexin-A is involved in activation of the HPA axis, and that these effects could be mediated via the release of NPY.     

Effects of metyrapone on hypothalamic-pituitary-adrenal axis and sleep in women with post-traumatic stress disorder.

BACKGROUND: Metyrapone blocks cortisol synthesis which results in removal of negative feedback, a stimulation of hypothalamic corticotropin releasing factor (CRF) and a reduction in delta sleep. We previously reported a diminished delta sleep and hypothalamic-pituitary-adrenal (HPA) response to metyrapone in men with post-traumatic stress disorder (PTSD). In this study, we aimed to extend these findings to women. METHODS: Three nights of polysomnography were obtained in 17 women with PTSD and 16 controls. On day 3, metyrapone was administered throughout the day up until bedtime. Plasma adrenocorticotropic hormone (ACTH), cortisol, and 11-deoxycortisol were obtained the morning following sleep recordings the day before and after metyrapone administration. RESULTS: There were no significant between-group differences in hormone concentration and delta sleep at baseline. Relative to controls, women with PTSD had decreased ACTH and delta sleep responses to metyrapone. Decline in delta sleep was associated with the magnitude of increase in ACTH across groups. CONCLUSIONS: Similar to our previous findings in men, the ACTH and sleep electroencephalogram response to metyrapone is attenuated in women with PTSD. These results are consistent with a model of downregulation of CRF receptors in an environment of chronically increased CRF activity or with enhanced negative feedback regulation in PTSD.     

Effects of Cysteamine Pretreatment and Hypothalamic Periventricular Nucleus Lesion on the Cold-Stimulated Thyrotropin Responses to Intracerebroventricular 5-Hydroxytryptamine in Male Rats

The hypothalamic somatostatinergic system was devitalized in male rats by intracerebroventricular (icv) cysteamine (CSH) pretreatment (250 μg/rat/day into the third ventricle) on 4 consecutive days or by a limited lesion of the hypothalamic periventricular nucleus (PeVNx). The acute effect of icv serotonin (5-HT) on the cold-stimulated thyrotropin (TSH) and prolactin responses were studied in these animals. The experiments were performed 24 h after the last saline or CSH infusions and 7 days after the sham- or PeVN-lesions. CSH and PeVNx decreased the hypothalamic somatostatin content by 44% to 57% and 19% to 28%, respectively. PeVNx did not affect hypothalamic thyrotropin-releasing hormone content. 5-HT infusion (9 μg/rat icv) into the anterior third ventricle elevated, although not significantly, TSH levels in both saline- or CSH-pretreated rats. 5-HT infusion into the anterior third ventricle did not affect TSH in sham-operated rats. However, 5-HT augmented the cold-stimulated TSH levels after PeVNx compared to sham-lesion. Inversely, 5-HT infusion (9 μg/rat) into the posterior third ventricle inhibited TSH secretion irrespective of the pretreatment or lesion. The inhibitory action of 5-HT on TSH was significantly suppressed by CSH. 5-HT infusions elevated serum prolactin levels irrespective of the infusion site, pretreatment or lesion. 5-HT infusion into both the anterior and the posterior third ventricle decreased rectal temperature in saline-pretreated, sham- and PeVN-lesioned rats. The hypothermie effect of 5-HT was weakened by CSH. The hypothalamic levels of noradrenaline, dopamine and their metabolites were not significantly affected by CSH and PeVNx. 5-HT infusion into the anterior third ventricle decreased hypothalamic dopamine content in both saline- and CSH-pretreated rats. However, such an effect was not seen in sham- or PeVN-lesioned animals. Although CSH is an inhibitor of dopamine-β-hydroxylase, this activity was not reflected in serum TSH or prolactin levels. The results support our hypothesis of the site-dependent action of icv 5-HT or TSH secretion. The elevation of TSH levels may arise from the inhibition of somatostatin release from rostral anterior hypothalamus. The inhibition of TSH secretion may result from the inhibition of thyrotropin-releasing hormone release from more caudal periventricular structures of the hypothalamus.     

Effects of a chronic exposure to a highly palatable diet and its withdrawal,in adulthood,on cerebral Na,K-ATPase and plasma S100B in neonatally handled rats

We have previously demonstrated that early environment influences the metabolic response, affecting abdominal fat deposition in adult female rats exposed to a long-term highly caloric diet. In the present study, our goal was to verify the effects of the chronic exposure, in adulthood, to a highly palatable diet (chocolate) on cerebral Na⁺,K⁺-ATPase activity and S100B protein concentrations, and the response to its withdrawal in neonatally handled and non-handled rats. We measured the consumption of foods (standard lab chow and chocolate), body weight gain, S100B protein concentrations, as well as cerebral Na⁺,K⁺-ATPase activity during chronic exposure and after chocolate withdrawal in adult female rats that had been exposed or not to neonatal handling (10 min/day, 10 first days of life). Non-handled rats chronically exposed to chocolate exhibited increased plasma S100B levels, but there was no difference in abdominal fat S100B concentration between groups. Chronic chocolate consumption decreased Na⁺,K⁺-ATPase activity in both amygdala and hippocampus in non-handled, but not in handled rats, and this effect disappeared after chocolate withdrawal. Non-handled animals also demonstrated increased frequency of head shaking in the open field after 24 h of chocolate withdrawal in comparison to handled ones. These findings suggest that neonatal handling modifies the vulnerability to metabolic and brain alterations induced by chronic exposure to a highly palatable diet in adulthood.     

Androgen and Estrogen Effects on Vasopressin Messenger RNA Expression in the Medial Amygdaloid Nucleus in Male and Female Rats

Vasopressin messenger RNA (AVP mRNA) expression in the medial amygdala and bed nucleus of the stria terminalis (BST) is almost completely dependent on gonadal steroids. In the BST, the effects of gonadal steroids on AVP mRNA expression are sexually dimorphic. Males have more cells that express AVP mRNA and more AVP mRNA per cell than females. Here we test whether this is also true for the MA. In gonadectomized rats that were treated with testosterone, males had more cells that were labeled for AVP mRNA than females. However, the labeling per cell did not differ between males and females. To assess contribution of testosterone metabolites to these differences, male and female rats were gonadectomized and implanted with empty tubing, or tubing filled with dihydrotestosterone (DHT), estradiol (E), or E plus DHT (E + DHT). The pattern of steroid effects on AVP mRNA expression in the MA was similar in both sexes. Hardly any labeled cells were found in rats with empty implants or rats treated with DHT. Significantly more labeled cells were found in rats treated with E, and even more cells in rats treated with E + DHT. The number of AVP mRNA-labeled cells was higher in males than in females for E as well as E + DHT treatment, but the labeling per cell did not differ between sexes. These data suggest that the number of MA cells that can express AVP mRNA is higher in males than in females, but the estrogen and androgen responsiveness of individual AVP mRNA-expressing cells in the MA does not differ between sexes.