Endocrine and behavioural responses to noise stress: comparison of virgin and lactating female rats during non-disrupted maternal activity

The behavioural and endocrine responses to a 10 min white noise stress have been characterized in female virgin and undisturbed lactating Sprague-Dawley rats. Animals were continuously video-taped and frequent blood samples were collected using an automated sampling system. Noise stress caused hypothalamo-pituitary-adrenal (HPA) activation, as indicated by a rapid increase in plasma corticosterone and ACTH in the virgins: corticosterone concentrations peaked 20 min after initiation of the stress before declining rapidly back to basal concentrations. In contrast, noise stress had no significant effect on either plasma corticosterone or ACTH concentrations in the lactating animals. However, 72 h after weaning the corticosterone response of the ex-lactating rats was of comparable magnitude, but longer duration to that seen in the virgins. Plasma prolactin concentrations were significantly higher in the lactating animals and declined in response to the noise whereas, a transient but reproducible increase was seen in the virgin group. In situ hybridization revealed a significantly lower basal expression of CRF mRNA in the paraventricular nucleus of lactating rats as compared to the virgins, but noise stress had no further effect. Virgin animals showed behavioural responses to the stress, including an increase in the total activity, exploratory behaviours (rearing) and displacement behaviours (grooming). Lactating animals also showed behavioural responses to the noise, but their activities were principally directed towards the pups. These data show that although lactating rats showed normal behavioural reactivity to a psychological stress they showed no statistically significant activation of the HPA axis, suggesting a dissociation of behavioural and neuroendocrine responses to this mild stress.     

Decline of maternal behavior in the virgin and lactating rat.

Gave to sensitized virgins and postpartum lactating mothers, both exhibiting maternal behavior, donor litters that increased in age by 1 day, for 28 days, starting at the onset of maternal behavior. Ss were 18 Charles River rats. Each day Ss were tested for maternal behavior with 4-8 day old pups. Maternal care (i.e., nursing-crouching, retrieving, nest building, and licking and maternal withdrawal, rejection, and prevention of nursing were recorded. After the 9th day, Ss were also tested with the progressively older pups 10-28 days of age with which they were living. Virgins and lactating mothers showed generally similar patterns of maternal care although some differences were found, and they declined in maternal behavior toward the older pups in a similar manner. Maternal behavior did not decline in tests with younger pups. Results are interpreted as supporting the hypothesis that the decline as well as the maintenance of maternal behavior postpartum is nonhormonally mediated. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory basis for the delayed onset of maternal behavior in virgin female rats: Experimental effects.

A previous study showed that intranasal zinc sulfate (ZnSO4) treatment shortens the latencies for the onset of maternal behavior in nonpregnant rats. The present study attempted to determine whether after recovery from the effects of ZnSO4 treatment, the latencies for maternal behavior increased. In Exp I, with 28 Charles River female rats, nonpregnant Ss were intranasally infused with ZnSO4 or air were left untreated and exposed to pups starting 48 hr later. Olfactory discrimination tests using chocolate bits were done simultaneously. The ZnSO4 treatment resulted in short latency maternal behavior (1.1 days) compared with latencies of control Ss (3.8 days), but neither group showed any loss of olfactory discrimination. 3 wks later, ZnSO4-treated Ss showed increased latencies for all but retrieving, while control groups showed decreased latencies for all maternal behaviors. In Exp II, with 13 nulliparous Charles River females, intranasal ZnSO4- and air-treated Ss were given olfactory discrimination tests under food deprivation, using chocolate bits and guinea pig pellets. Choice of guinea pig pellets was more severely affected than choice of chocolate bits, but recovery of the discriminations was complete in 4-5 days. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prenatal exposure to methylmercury alters locomotor activity of male but not female rats

In the present study the neurotoxic effects of a low dosage (0.5 mg/kg per day) of methylmercury (MeHg) on the developing nervous system were investigated. Pregnant rats were treated with MeHg from day 7 of pregnancy to day 7 of lactation. Locomotor activity (locomotion, rearing, and motility) and spatial learning ability were tested in the offspring at 6 months of age. The expression of tyrosine hydroxylase (TH) was examined by immunohistochemistry and in situ hybridization. A significant decrease in spontaneous motility and rearing was observed only in the MeHg-treated male rats. After administration of a low dose of d-amphetamine (0.5 mg/kg) no differences could be observed between control and MeHg-treated male rats, suggesting that changes in dopaminergic transmission were involved. However, no change in TH messenger RNA expression was observed. No changes in spatial learning acquisition or memory were shown in MeHg-treated rats. Taken together, these findings show that during development a very low dosage of MeHg exerts neurotoxic effects detectable in adulthood, and that susceptibility is gender-dependent.     

Dissociation of novelty- and cocaine-conditioned locomotor activity from cocaine place conditioning

This study investigated a total number of 120 colorectal malignant tumor tissues by applying a new quantitative luminometric assay (LIA)-mat, immunohistochemistry (IHC) (n=100), PCR/SSCP (n=42), and sequencing (n=7). Sera were collected from 235 patients suffering from colorectal carcinoma in addition to 195 healthy individuals as a control group. Manual ELISA kit was developed to detect p53 autoantibodies in the sera of those patients. Our data demonstrated that the LIA-mat yields reliable estimates of p53 expression in soluble cell extracts as compared with results obtained by immunohistochemistry which showed positive immunostaining in 63% of the studied cases. Using a cut-off value of 1.8 ng/mg protein, 65 tumors out of 120 (54%) were classified to be positive by LIA-mat, manifesting protein overexpression, while 22 out of 42 (52%) tumor samples showed p53 gene alteration when applying single strand conformation polymorphism (SSCP) analysis on polymerase chain reaction products. In tumor samples without a p53 gene alteration, the median soluble p53 protein level was 4.3 ng/mg protein, whereas the median p53 protein level for tumor samples with p53 gene alteration was 7.5 times higher. Despite a significant correlation between the outcome of LIA and SSCP, a disagreement was found in 30% of cases. We found no significant correlation between p53 protein overexpression and clinicopathological findings except for distant metastasis (p=0.33), indicating p53 immunoreactivity to be an independent prognostic factor. Our data showed that 18% of patients suffering from colorectal cancer developed autoantibodies against p53 in their sera which might be an early indicator for tumor development and distant metastasis.     

Maternal behavior in the virgin and lactating rat.

Observed the onset of maternal behavior in 20 Sprague-Dawley virgin female rats during pup induction, and later compared their behavior with that of 8 lactating mothers. During induction, the onset was sudden rather than gradual, and during maternal care their behavior was similar in almost all respects to that of lactating mothers. Reinduction of maternal behavior in virgins occurred with a shorter latency than during the original induction, and induction of maternal behavior in formerly lactating mothers was equally short. Results support the idea that postpartum maternal behavior is nonhormonally based. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Repeated neonatal maternal separation alters intravenous cocaine self-administration in adult rats

Behavioural responses to psychostimulant drugs can be profoundly affected by early environmental influences. The aim of this study was to describe the effects of repeated brief separations of rat pups from their dams during the early neonatal period on cocaine self-administration behaviour as adults. Lister hooded rats exposed to a repeated maternal separation procedure (REMS) showed altered acquisition and maintenance of cocaine self-administration as adults, the effects being dose and gender-dependent. Overall, the patterns of acquisition of self-administration across three doses of cocaine (0.05, 0.08 and 0.5 mg/injection) suggested a rightward shift in the acquisition dose-effect functions for the REMS animals relative to control animals. At 0.05 mg/injection, there was a retarded acquisition of cocaine self-administration in male and female neonatally separated rats. At 0.08 mg/injection there was a facilitated acquisition in female neonatally separated subjects. After establishment of stable self-administration of the training dose, in the same cohort of subjects, rightward and downward shifts in the cocaine self-administration dose-effect functions were determined for female and male REMS subjects, respectively, relative to their controls. The dose-effect function for both female groups was shifted to the left of that of the respective male groups, although the lighter body weights of the females meant that they administered a higher unit dose per unit body weight than the males. Whereas male REMS subjects tended to self-administer less cocaine than the controls at the dose eliciting maximal responding (0.03 mg/injection) and to make fewer lever responses overall at each dose tested, female REMS subjects self-administered significantly more cocaine than their respective controls at a dose of 0.03 mg/injection. There was no differential sensitivity to the rate-altering effects of the selective dopamine D2 receptor antagonist, eticlopride, or to the selective dopamine D1 receptor antagonist, SCH 23390. These data provide further evidence that altered early environment affects drug-taking behaviour in a developmentally specific and gender-specific manner, with the effects of neonatal separation contrasting with previously published data on the effects of post-weaning isolation rearing.     

Plasma somatomedin activity, growth-hormone and insulin levels in vitamin B6 deficient rats

Plasma somatomedin activity was low in rats fed a vitamin B6 deficient diet for 4 weeks. The reduction appears to be in the fraction which is not growth hormone dependent. Plasma growth hormone levels were unaltered while plasma insulin levels were significantly reduced.     

Dopamine infusion does not alter LH levels before or after chronic cocaine exposure in female rhesus monkeys

Cocaine stimulates release of luteinizing hormone (LH) in preclinical and clinical studies but the contribution of the indirect dopamine agonist actions of cocaine to its effects on LH are unclear. In the present study, we examined the effects of exogenous dopamine infusions on LH release in drug-naive, normally cycling, female rhesus monkeys. All studies were conducted during the mid-follicular phase (cycle days 6-8). Three successive 80-min dopamine infusions (10 micrograms/kg/min, intravenous) were alternated with 20- or 40-min interruptions of dopamine infusions. There were no significant changes in LH during or following dopamine infusions. Predopamine baseline LH levels averaged 30 +/- 5.4 ng/ml. LH averaged 31.7 +/- 1.3 ng/ml during dopamine infusions and 31.4 +/- 1.3 ng/ml after dopamine infusions stopped. To determine whether chronic cocaine exposure influenced the effect of dopamine on LH, rhesus females were studied after more than 2 years of cocaine self-administration at an average dose of 6.5 +/- 0.2 mg/kg/day. LH averaged 27.3 +/- 3.3 ng/ml during baseline and 26.9 +/- 0.7 ng/ml and 26.1 +/- 0.7 ng/ml during dopamine infusions and interruptions, respectively. Similarly, during withdrawal from cocaine, baseline LH levels averaged 32.1 +/- 4.5 ng/ml, and LH did not change significantly during dopamine infusions (31.2 +/- 1.1 ng/ml) and infusion interruptions (32.1 +/- 1.1 ng/ml). Under the conditions of the present study, dopamine administration did not change LH levels in gonadally intact rhesus monkeys, and these findings are consistent with previous studies in ovariectomized rhesus females. However, these data are not consistent with clinical reports, and some possible implications of this species difference are discussed. Moreover, these data suggest that the stimulation of LH by cocaine may not be explained by its indirect dopamine agonist actions.     

Selective retrieving by maternal and nonmaternal female rats.

Conducted an investigation to learn whether nonpregnant female rats made maternal by exposure to pups would act more like nonmaternal females than lactating mothers. Ss were 32 nulliparous females of the Charles River CD strain and an additional number of females that provided pups for inducing maternal behavior in virgins and in testing all Ss in pup vs toy tests. The behavior toward a pup and a toy was studied in 1 group of nonmaternal virgins, 2 groups of maternal virgins, and 1 group of lactating mothers, during 7 daily 5-min tests. Measures of the frequency and duration of retrieving-related behavior and analysis of behavioral sequences in relation to the pup or toy showed that pup-induced maternal virgins more closely resemble the lactating mothers than nonmaternal virgins. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Plasma apolipoprotein profiles of male and female rats

To determine if sex differences exist in the apolipoprotein profile of the rat, the concentrations of the major apolipoproteins and lipids of 12-week-old male and female rats were measured in the plasma as well as in the individual lipoprotein fractions. Plasma apo B, triglyceride, and cholesterol concentrations were significantly higher in male rats than in female rats. Plasma concentrations of apo A-I, apo E, apo A-IV, and apo C-III did not differ between the sexes. Male rats had higher concentrations of apo B in the very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and the low density lipoproteins (LDL). These results further support the evidence that sex hormones influence lipoprotein metabolism in the rat.     

Age-related impairment of food anticipatory locomotor activity in rats

In rats of various ages (11 weeks to 24 months), restricted feeding was carried for 6 successive days and food was withheld completely on the 7th day to assess the effect of aging on food anticipatory activity. When feeding was restricted to a single meal at a fixed time of day (1330-1730), rats exhibited intense locomotor activity from 1-3 h before feeding time (prefeeding activity). This prefeeding activity was still detected on the fasting day. In addition, intense locomotor activity was observed for 1330-1730 even on the fasting day (mealtime-associated activity). Thus, mealtime-associated activity of the fasting day became an another good index for food anticipatory activity. These results indicate that the rats had come to anticipate the mealtime. Both prefeeding and mealtime-associated activities were similar at 11 weeks and 9 months of age, but they were impaired at 12 and 24 months of age. In 11-week-old rats, there was a negative correlation between the level of mealtime-associated activity and the daily duration of access to food, but this relationship was absent in 12-month-old rats. The present study suggests that aging strongly impairs the manifestation of food anticipatory activity in rats.     

Proestrous gonadotropin levels in thyroparathyroidectomized female rats

Intact and TPTx animals showed the expected afternoon increase in serum LH,FSH and prolactin levels. But the afternoon increase in serum LH levels in TPTx rats was less than that observed for intact animals (p less than 0.001). Neither serum prolactin nor FSH levels were altered by TPTx.     

Intact neurons of the lateral habenular nucleus are necessary for the nonhormonal, pup-mediated display of maternal behavior in sensitized virgin female rats

Our research has demonstrated that the lateral habenular nucleus (Lhb) is necessary for the hormonal onset but not the postpartum maintenance of maternal behavior in the rat (K. P. Corodimas, J. S. Rosenblatt, & J. I. Morrell, 1992; K. P. Corodimas, J. S. Rosenblatt, M. E. Canfield, & J. I. Morell, 1993; T. Matthews-Felton, K. P. Corodimas, J. S. Rosenblatt, & J. I. Morell, 1995). To test the role of the Lhb in the nonhormonal onset of maternal behavior, we used the sensitization model in which the continual exposure of females to pups induces maternal behavior. Ovariectomized females received bilateral cytotoxic lesions of neurons of either the Lhb or the dorsal medial cingulate cortex-hippocampus, or they were unoperated. Maternal behavior, activity, and oromotor carrying capability were tested. Complete lesions of the neurons of the Lhb induced significant deficits in pup retrieval and nest building. Sniffing, licking, and crouching behaviors were unaltered. Activity and carrying ability were normal. These results indicate a role for the Lhb that extends to the nonhormonally dependent onset of maternal behavior, but they also indicate a more limited role than in the mediation of the hormonal onset of the behavior.     

Effects of feeding medium-chain triacylglycerols on maternal lipid metabolism and pup growth in lactating rats

To study the effects of medium-chain triacylglycerols (MCT) on maternal lipid metabolism and pup growth, MCT (200 g/kg) were incorporated into a commercial chow diet and fed to lactating rats for 8-10 d. The results were compared with similar diets containing sunflower oil (polyunsaturated fatty acids; PUFA), tristearin (saturated fatty acid) or triolein (monounsaturated fatty acid). There was decreased food and energy intake with the MCT diet and this was accompanied by decreased (35%) pup growth. All the high-fat diets inhibited lipogenesis in vivo in the lactating mammary gland, the order of effectiveness being PUFA > triolein > tristearin > MCT. Only the MCT diet increased the rate of hepatic lipogenesis (180%). Experiments feeding an MCT meal containing [1-14C]octanoate indicated that very little (3-4%) of the C was present in mammary gland lipid, unlike the findings with [1-14C]triolein meal (40%). The major portion (65%) of the absorbed [1-14C]octanoate was oxidized to 14CO2. There was no evidence for adaptation of the mammary gland to increased dietary lipid uptake on the triolein or MCT diets. It is concluded that the decreased pup growth on the MCT diet is due in part to the decreased energy intake and to the inability of dietary medium-chain fatty acids to provide substrates for milk lipid synthesis.     

Alterations in locomotor activity during chronic cocaine administration: effect on dopamine receptors and interaction with opioids

Chronic cocaine administration can produce tolerance or sensitization to locomotor activating effects, depending on the treatment paradigm. The effects of chronic, continuous cocaine were measured on locomotor activity for 1 hr daily for 7 days. Cocaine produced significant increases in locomotor activity 4 hr after osmotic minipumps were implanted, and an even higher level of activity after 24 hr. This was likely a rapid sensitization to the locomotor activating effects of cocaine, because neither brain nor plasma levels of cocaine were significantly altered over the treatment period. By day 4, activity levels diminished, but remained significantly higher than in saline-treated animals. Twenty-four hr after pump removal, there were no changes in dopamine D1 or D2 receptor binding, or in dopamine-stimulation of adenylyl cyclase activity in either caudate putamen or nucleus accumbens of cocaine-treated animals. Chronic naltrexone produced a slight, nonsignificant decrease in locomotor activity and when combined with cocaine, produced the same pattern of activity as cocaine alone, but with slightly less stimulation on all days. Morphine produced a smaller increase in activity than cocaine that remained constant throughout the treatment week. Cocaine with morphine was additive, producing greater activity and less tolerance than cocaine alone. Thus, continuous cocaine administration produces a rapid sensitization that is lost over the course of the treatment period, yet does not produce any immediate alterations in dopamine receptors or regulation of adenylyl cyclase. The pattern of behavior is not altered by an opioid antagonist, while the sensitization period appears to be prolonged in the presence of an opioid agonist.     

Plasma levels of clonidine following epidural bolus injection in children

PURPOSE: To describe dense vitritis as the primary manifestation of ocular syphilis in three human immunodeficiency virus (HIV)-positive patients and to determine the response of these patients to the established regimen for neurosyphilis. METHODS: Anti-Toxoplasma gondii IgM and IgG antibody titers, tuberculin skin test, chest radiograph, and serum angiotensin-converting enzyme level were obtained because tuberculosis, sarcoidosis, and toxoplasmosis were in the differential diagnosis. Two of the three patients were not known to have HIV infection at the time of initial examination and consented to HIV testing. Treponemal and nontreponemal tests were performed on serum and cerebrospinal fluid to establish a definitive diagnosis. Treatment for neurosyphilis was initiated, and daily ophthalmic examinations were performed, with careful attention to signs commonly associated with syphilitic eye disease. RESULTS: All three patients exhibited improvement in visual acuity and resolution of vitreous haze. There was no evidence of other signs of posterior uveitis. The one patient for whom there has been a 6-month follow-up showed no sequelae of his eye disease. CONCLUSIONS: Human immunodeficiency virus-positive patients with syphilis may present atypically dense vitritis. In these patients, vitritis may be the first manifestation of syphilis. The regimen for neurosyphilis provides effective therapy. Moreover, in some patients, syphilitic vitritis may be the initial manifestation of HIV disease.     

Modulation of phencyclidine-induced changes in locomotor activity and patterns in rats by serotonin

Membrane-expressed immunoglobulins are B-cell receptors (BCR) for specific antigens (Ag). Upon Ag engagement of the BCR, B-cells are activated to internalize Ag-BCR complexes, process Ag and subsequently present Ag-peptides loaded in class II MHC. Due to the specific nature of the BCR, the cognate interaction between T-cells expressing Ag-specific T-cell receptor and these Ag-presenting B-cells occur in a highly regulated and precise manner. Accordingly, efficient control of T-cell activation may be achieved through regulation of Ag presenting B-cells. A potent form of regulation of lymphocyte responses is mediated by Ig end-product and anti-idiotypic antibodies via Fc-dependent mechanisms. In this communication, the authors present data that an anti-idiotype (anti-Id) Ab inhibits BCR-mediated internalization of specific Ag. Coupling of BCR to the cytoskeleton was also abortive in anti-Id Ab-treated B-cells. Inhibition by anti-Id Ab was dependent upon the presence of FcgammaRIIB1 on B-cells. As a result of anti-Id Ab suppression, B-cells were unable to initiate Ca2+ responses in Ag-specific T-cells. The results suggest that co-crosslinking of FcgammaRIIB1 and BCR inhibits cytoskeletal coupling and internalization of the Ag-BCR complex thereby preventing specific Ag presentation by B-cells. Anti-Id Ab may mediate a negative regulatory mechanism that suppresses B-cell-mediated Ag-specific T-cell activation.     

Determination of the place conditioning and locomotor effects of amperozide in rats: A comparison with cocaine.

Amperozide promotes social interactions in rats (Rattus norvegicus) and reduces craving for cocaine and alcohol without producing adverse side effects. Amperozide administration produced a place preference in the dose range from 3.0 to 10.0 mg/kg. Locomotor behavior tended to be suppressed on the days of amperozide pairings, elevated on the days of vehicle pairings, and elevated on test days. Administration of 20.0 mg/kg but neither 2.0 nor 0.2 mg/kg cocaine produced place preference. Rats exhibited a greater place preference for the chamber paired with 2.0 mg/kg and 20.0 mg/kg but not 0.2 mg/kg cocaine compared to the chamber paired with 5.0 mg/kg amperozide. The results indicate that amperozide is appetitive. The most appetitive dose of amperozide (5.0 mg/kg) is less appetitive than the most appetitive dose of cocaine (20.0 mg/kg). More research is needed before conclusions regarding the degree of abuse potential for amperozide can be made. (PsycINFO Database Record (c) 2010 APA, all rights reserved)