Cellular response to an intravascular catheter.

Central venous catheters are commonly used in clinics for the administration of infusion therapy and total parenteral nutrition. Catheter occlusion is the most common noninfectious complication associated with the long-term use of such devices. The cause of catheter occlusion is the formation of a tissue sleeve around the catheter. In this study, a rat model was used to investigate the effects of integrin antagonist peptide on the growth of the tissue sleeve around the jugular catheters. When integrin antagonist peptide was injected subcutaneously, twice daily, for 3 days, at a dosage of 10 mg/kg of body weight/day, the growth of the tissue sleeve was reduced by 40%, as compared to rats injected with saline or control peptide. Morphological study of the tissue sleeve indicated that catheter-related damage to the nearby endothelial cells was associated with the adhesion of platelets and leukocytes to the injured endothelium and accumulation of fibrin in the vicinity. This proposed sequence of events resulted in an increase in the thickness of the tissue sleeve and changes in sleeve transparency.

Plasma interleukin-1beta, prolactin, ACTH and corticosterone responses to endotoxin after damage of the anterior hypothalamic area.

This report concerns the use of an animal model described by us [J Submicrosc Cytol Pathol 1995;27:83-89] to investigate neural and endocrine sites for endotoxin (ENDO, E. coli 055:B5, 200 microg/100 g body weight in saline intravenously) effects on immunomodulatory hormone and cytokine release. Plasma interleukin-1beta (IL-1beta), prolactin (PRL), ACTH and corticosterone responses to ENDO after neurotoxic damage of neurons residing in the anterior hypothalamic area (AHA) were studied in freely behaving male rats. Excitotoxic cell damage in the AHA was produced by bilaterally injecting N-methyl-DL-aspartate (NMA) in artificial cerebrospinal fluid (aCSF) into this brain site. Injections of comparable volumes of aCSF alone served as controls for brain damage associated with the treatment. In both experimental brain manipulations before ENDO challenge the rise in plasma IL-1beta concentrations in response to ENDO was reduced by 2-fold at 1 h and 3- to 5-fold at 3 h when compared to controls. Nevertheless, experimental and control brain manipulations did not modulate the expected rise in corticosterone concentrations after ENDO exposure which rose 5-fold above the baseline level in all animals. However, AHA manipulation did reduce plasma ACTH and prolactin concentrations differentially. Introduction of either NMA or the control injection of aCSF alone into AHA reduced plasma ACTH concentrations by 2-fold at 0.5 and 1 h after ENDO. However, there was a greater reduction in the rise of plasma PRL concentrations after ENDO found in NMA-treated groups versus rats receiving control aCSF. These results demonstrate that variable-size hypothalamic damage (a larger lesion produced in AHA by NMA treatment vs. a smaller lesion control after aCSF) can result in a differential blunting of PRL, IL-1beta and ACTH release into blood in the face of robust, unmodulated corticosterone increases. In summary, these findings revealed a consistent predominant influence of ENDO on adrenal release of corticosterone as a concomitant to differential IL-1beta, ACTH and PRL release after AHA cell loss. In conclusion, these results constitute further evidence for hypothalamic orchestration of a balance between immunotropic and immunosuppressive neuroendocrine-immune events during acute bacterial infection of mammals.

Cytokine and adrenal axis responses to endotoxin.

The push-pull cannula (PPC) technique was applied to examine the kinetics of in vivo concentration changes in male rat brain extracellular fluid (ECF) of endogenous interleukin-1beta (IL-1beta) and corticotrophin releasing hormone (CRH) after a peripheral injection of lipopolysaccharide (LPS) (25 microg/100 g b.wt. intravenously). In addition, IL-1beta, adrenocorticotropin hormone (ACTH) and corticosterone concentrations in plasma were also measured at selected intervals after LPS challenge. Administration of LPS resulted in a progressive increase in the concentrations of IL-1beta in brain hypothalamic ECF. A significant increase from the zero time mean value of 77+/-10 to 393+/-88 pg/ml at the 15-min interval was recorded. The increase in IL-1beta concentration in hypothalamic ECF reached a peak of 883+/-237 pg/ml at 30 min post-LPS. CRH concentration in the same hypothalamic ECF was 41+/-17 pg/ml at time zero, 97+/-15 pg/ml at 15 min and at 30 min was significantly increased (215+/-56 pg/ml). A time course of significant increases at 30 min in plasma concentrations of IL-1beta, ACTH and corticosterone was also recorded in the same animals described above. The data show that a peripherally administered LPS bolus elicited an early (over 15 min post-injection) increase in brain ECF IL-1beta concentration; additional significant increases in hormones released from the hypothalamic-pituitary-adrenal (HPA) axis were recorded at 30 min post-LPS injection. These observations support the concept of an early change in hypothalamic ECF concentration of IL-1beta preceding LPS-induced activation of the HPA axis.

In ovo peptide YY administration improves growth and feed conversion ratios in week-old broiler chicks.

The effects of in ovo Peptide YY (PYY) administration on growth and feed conversion ratios in a commercial broiler line were investigated. Six hundred Ross male x Cobb female eggs were administered either 0.9% saline (control) or 600 microg/kg egg weight PYY in ovo at Day 18 of incubation. On day of hatching, 210 birds from each treatment group were randomly placed by sex into pens. Body weights at placement were not different between treatment groups. Average chick body weight and adjusted pen feed conversion ratios were improved by PYY in ovo treatment at 7 d posthatch (165.7 vs. 170.2 g, P<0.02; and 1.55 vs. 1.49, P<0.04, respectively). No significant differences between treatments were noted for these parameters at 21 or 42 d of age. These results suggest that in ovo treatment of broiler chicken eggs with gastrointestinal hormones that increase intestinal nutrient absorption, such as PYY, may enhance chick performance.

Maternal diet fatty acid composition affects neurodevelopment in rat pups.

The effect of pre- and postnatal maternal dietary fatty acid composition on neurodevelopment in rat pups was studied. Timed pregnant dams were fed, beginning on d 2 of gestation and throughout lactation, either nonpurified diet (reference) or a purified diet whose fat source (22% of energy) was either corn oil or menhaden fish oil. On postnatal d 3, pups were randomly cross-fostered among dams of the same diet group and culled to 10 pups per dam. Milk was removed from stomachs of culled pups for fatty acid analyses. From postnatal d 4 to 30, pups were assessed daily for the appearance of neurodevelopmental reflexes. Auditory brainstem conduction times were measured on postnatal d 23 and 29. Pups were killed on postnatal d 30, and cerebrums were removed for fatty acid analyses. The fatty acid composition of maternal milk and pup cerebrums reflected maternal diet with higher levels of (n-3) and (n-6) fatty acids in the fish oil and corn oil groups, respectively. The time of appearance of auditory startle was significantly delayed (P = 0.004), and auditory brainstem conduction times on postnatal d 23 and 29 were significantly longer in pups of the fish oil- than corn oil-fed dams (P

Insulin and insulin-like growth factor II suppress neuropeptide Y release from the nerve terminals in the paraventricular nucleus: a putative hypothalamic site for energy homeostasis.

It has been recently recognized that a distinct signaling pathway in the hypothalamus is involved in the stimulation of feeding in mammals. Neuropeptide Y (NPY), a member of the pancreatic polypeptide family, is the most potent orexigenic signal, and its secretion in discrete hypothalamic sites increases in response to insulinopenia produced by food deprivation or experimental diabetes. To establish the site of interaction between the hypothalamus and the pancreas, we examined the effects of insulin on NPY release in vivo and in vitro from hypothalamic sites known to be involved in feeding behavior. In the first study we evaluated the effects of peripheral insulin injections (1 U/kg.day, sc) on NPY levels in seven hypothalamic nuclei in food-deprived (FD) and ad libitum-fed rats. Whereas food deprivation for 3 days increased NPY levels in the medial preoptic area, paraventricular nucleus (PVN), and arcuate nucleus, insulin injections, which did not alter blood glucose levels, returned NPY levels to the control range selectively in the PVN. NPY levels in the hypothalamic nuclei remained unchanged after insulin injections in ad libitum-fed rats. The in vivo NPY release in the PVN of FD rats, evaluated by the push-pull cannula technique, also decreased in response to peripheral insulin injections. Finally, the effects of insulin, insulin-like growth factor I (IGF-I), and IGF-II on NPY release in vitro from the microdissected PVN and two central neighboring sites, the ventromedial nucleus and the median eminence-arcuate nucleus, of FD rats were evaluated. Both insulin (0.67 or 6.7 nM) and IGF-II (0.7 or 7.0 nM) decreased the release of NPY in a dose-dependent manner only from the PVN. On the other hand, IGF-I (0.07 or 7.0 nM) failed to alter the basal PVN NPY efflux. As the PVN is richly innervated by NPY-containing nerve terminals, the results of these in vivo and in vitro studies suggest that the site of insulin action on the hypothalamic NPY network may reside at the level of PVN nerve terminals or at the interneurons in contact with NPY nerve terminals. Although insulin may have a direct effect in reducing NPY release from the PVN, the effectiveness of IGF-II in decreasing NPY release from the PVN raises the possibility that insulin's action may also be mediated via hypothalamic IGF-II neuronal pathways.

In vivo release of interleukin-1 beta into hypothalamic extracellular fluid in rats: effects of repeated sampling.

Interleukin-1 beta (Il-1 beta) concentrations in extracellular fluid (ECF) withdrawn at 10-min intervals through a push-pull cannula (PPC) located in the hypothalamus were studied in freely behaving male rats for 1 h at 24 and 72 h and again at 7 days after PPC implantation. Il-1 beta concentrations in ECF were similar in the latter. However, when ECF was sampled at 3 h and again 7 days after PPC implantation, Il-1 beta concentrations were greatly elevated at 7 days when compared to all other intervals. These results demonstrate how the relationships between Il-1 beta measured in ECF and the conditions of measurement appear to be integral parts of a whole intracerebral system: cytokine concentrations appear to be inextricably bound to intrahypothalamic conditions created by the sampling device presence and frequency of use.

Variable tissue reactions and endocrine responses to a jugular catheter.

Although the use of soft catheter materials allows for safe long-term venous access in humans and animals, a significant percentage of individuals react adversely. We have studied a group of 52 male rats over 30 days (d) for the category and degree of tissue responses to silicone-based catheters implanted in the jugular vein. Included in this evaluation was blood withdrawal at multiple intervals for assay of plasma hormones corticosterone (CORT) and prolactin (PRL) as they were correlated with the immune phenomena associated with early (5-7d) obstruction of the catheter tip. The intravascular portion of all catheters were covered with a transparent sheath which was composed of endothelial cells, smooth muscle cells, fibroblasts and numerous collagen fibers. Early blockage of catheters was the result of large white masses (wm) enclosing the tip which were continuous with the sheath. The wm consisted of: a) an inner zone nearest the catheter in some regions predominantly composed of numerous platelets and in others granulocytes and platelets; b) a middle zone containing numerous neutrophils; c) an outer zone containing a few inflammatory cells and many spaces filled with red blood cells. Rats that developed a wm blockage 7-10d after catheter placement had higher plasma CORT levels (3-5d post implant) when compared to those of animals with catheters remaining open 3-4 weeks. When viewed together, these observations describe a subset of a larger population of rats that have a local intravascular inflammatory reaction to silicone-based catheters. This preparation may be a useful model for investigating reported differences in human reactivity to silicone-based prostheses.

How does the brain know the body is sick? New approaches to an old problem in medicine.

The physiological significance of a widespread distribution of lymphoid cells throughout most of the organ systems in the body is thought to represent the general tissue requirement for protection and vigilance against foreign invaders and certain other disease states. More recently, this distribution has also been viewed as a group of immune system transducers capable of extending the sensory capabilities of the central nervous system. The information monitors the internal state of the body in relation to the external environment including potential invaders, malignant transformations of body cells, and certain other disease-causing agents. This kind of information is clearly on a sensory scale or wavelength not otherwise available to the central nervous system. The information consists of chemical messengers rather than energy, which is monitored by sensory pathways that have been conceptualized and studied over a much longer period of time.

Neuropeptide Y release from the paraventricular nucleus increases in association with hyperphagia in streptozotocin-induced diabetic rats.

We tested the hypothesis that the hyperphagia observed in streptozotocin (STZ)-induced diabetic rats is due to increased release of neuropeptide Y (NPY) in the paraventricular nucleus (PVN) of the hypothalamus. In the first experiment, male rats were injected with STZ or vehicle (control) via the tail vein and 18-20 days later, NPY levels in seven hypothalamic sites and release in vitro from selected hypothalamic sites were evaluated. The results showed that in association with STZ-produced marked hyperglycemia and hyperphagia, NPY concentrations were increased in four hypothalamic sites, including the PVN. Evaluation of NPY release in vitro showed that both basal and KCl-induced release was significantly higher from the micro-dissected PVN of STZ-treated than control rats. A similar augmentation in the NPY efflux in vitro was detected from the median eminence arcuate nucleus, but not from the neighboring ventromedial nucleus of STZ-treated rats. In the second experiment, rats were treated with STZ or vehicle and received permanent push-pull cannula (PPC) in the PVN for evaluation of NPY release in vivo 18-21 days after STZ treatment. The results showed that mean NPY levels in the perfusates collected from the PVN of diabetic rats were significantly higher as compared to control rats. Since NPY is the most potent naturally occurring orexigenic signal and the PVN is an important initial site of NPY action in the stimulatory pathway regulating feeding, our findings of augmented PVN NPY release in vivo and in vitro are in accord with the hypothesis that increased NPY secretion in the PVN may be responsible for hyperphagia in diabetic rats.

Effect of d-fenfluramine on neuropeptide Y concentration and release in the paraventricular nucleus of food-deprived rats.

Recent evidence indicates that Neuropeptide Y (NPY) is an important signal in the hypothalamic neural circuitry that stimulates feeding in the rat. Administration of d-fenfluramine (FEN) has been shown to rapidly inhibit feeding in the rat. Because food deprivation increases the levels and release of NPY in the paraventricular nucleus (PVN) of the hypothalamus, the aim of this study was to investigate whether the rapid anorectic effects of FEN in food-deprived (FD) rats are associated with alterations in the hypothalamic NPYergic system. In the first experiment, the effect of FEN (10 mg/kg) on NPY concentrations in nine microdissected hypothalamic sites was assessed by radioimmunoassay (RIA) in rats either food deprived for 3 days or fed ad lib during the experimental period. In response to food deprivation, NPY concentrations increased significantly in the PVN and arcuate nucleus, but NPY levels remained unchanged in the remaining seven hypothalamic sites. In control rats maintained on ad lib food supply, FEN injection produced little effect on NPY concentration in hypothalamic sites. However, FEN suppressed NPY levels selectively in the PVN of FD rats, so that NPY concentrations measured in the nucleus were within the range found in satiated control rats. In the second experiment, the effect of FEN on NPY release in the PVN was examined in FD rats by the push-pull cannula (PPC) technique. NPY levels in the PPC perfusate were unchanged in FD rats during the period 30-120 min after saline or FEN injection. Also, the mean rate of NPY release was similar in vehicle- and FEN-treated FD rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Steroidal regulation of hypothalamic neuropeptide Y release and gene expression.

Neuropeptide Y (NPY) readily stimulates the release of hypothalamic LHRH and pituitary LH release in intact and gonadal steroid-primed gonadectomized rats. We have now tested the hypothesis that the release and synthesis of hypothalamic NPY may be regulated by gonadal steroids. To measure the effects of gonadal hormones on NPY release, a permanent push-pull cannula was implanted in the anterior pituitary (AP) of sham castrated (controls) or castrated (CAST) male rats, and 1 week later, the AP was perfused with artificial cerebrospinal fluid over a 3-4 h period. NPY concentrations in the perfusates collected at 10-min intervals were measured by RIAs. The NPY release pattern in the AP was episodic in both intact and CAST rats, and the frequency of NPY episodes was similar in two groups. However, the amount of NPY detected in the AP of CAST rats was significantly less than that of intact rats because the mean rate of release and the amplitude of NPY episodes in the perfusates of CAST rats were significantly reduced. This observation of attenuated hypothalamic NPY output in vivo and previous evidence of decreased hypothalamic NPY contents after CAST implied that the synthesis of hypothalamic NPY may be regulated by testicular secretions. Therefore, the effects of testosterone (T)-replacement on preproNPY messenger RNA (mRNA) in the medial basal hypothalamus (MBH) was evaluated. Rats were CAST and received either empty or T-filled Silastic capsules sc. Two weeks later, the level of perproNPY mRNA in the MBH was determined by solution hybridization/ribonuclease protection assay using a complementary RNA probe complementary to the rat NPY precursor mRNA. We observed that the levels of preproNPY mRNA were 2-fold higher in the MBH of T-replaced CAST as compared to control CAST rats. These findings are consistent with the hypothesis that gonadal steroids enhance the neurosecretory activity of hypothalamic NPYergic neurons, and for the first time reveal a coupling between the level of gene expression and the secretion of a neuropeptide involved in the regulation of hypothalamic LHRH and pituitary LH release.

In vivo pulsatile LHRH release into the anterior pituitary of the male rat: effects of castration.

The effects of castration on the concentration of luteinizing hormone releasing hormone (LHRH) in the anterior pituitary (PIT) was studied in freely-behaving male rats using a push-pull cannula for sampling. In over 70 perfusions of the PIT of rats sampled before and at multiple days after castration there was no consistent change detected in the overall amount, secretory pulse amplitude or frequency or the LHRH signal reaching the PIT.

Neuropeptide Y secretion increases in the paraventricular nucleus in association with increased appetite for food.

Feeding in mammals is a periodic behavior; however, knowledge of how the brain signals an intermittent eating pattern is scanty. Recent indirect evidence indicates that one of the signals encoded in the structure of neuropeptide Y (NPY) is to stimulate robust feeding. Therefore, two series of experiments were undertaken to characterize NPY secretion within the paraventricular nucleus (PVN) in association with eating behavior in the rat. Dynamic changes in NPY concentration in several hypothalamic sites and release in the PVN were assessed before and during the course of food consumption in rats trained to eat daily only for 4 h. Only in the PVN were NPY concentrations elevated before the introduction of food and, thereafter, levels decreased significantly during the course of eating. A similar temporal pattern in NPY release into the PVN interstitium was evident in samples collected by push-pull cannula perfusion in unrestrained rats. In addition, in food-deprived rats displaying a robust drive for feeding, NPY release in the PVN was also markedly enhanced in the shape of high-amplitude secretory episodes as compared to a lower release rate in rats receiving food ad libitum. The higher rate of NPY release in fasted rats returned to the control range after 24 h of ad libitum food supply. These findings of intense and dynamic NPY neurosecretory activity within a discrete hypothalamic site in association with an increased drive for food consumption demonstrate that NPY release in the PVN is an important orexigenic signal for periodic eating behavior. These results have important global implications for elucidating the underlying causes of the pathophysiology of eating disorders--anorexia nervosa, bulimia, and obesity--as well as constituting a specific contextual model for the formulation and testing of suitable NPY receptor agonists and antagonists for therapeutic intervention.

The effect of prior surgical disconnection of the anterior mediobasal hypothalamus on LHRH release in vitro.

The degenerative responses of luteinizing hormone-releasing hormone (LHRH)-containing neurons within the mediobasal hypothalamus (MBH) after knife cut lesions (FC) made in the frontal plane of the retrochiasmatic hypothalamus include a reduced number of LHRH-immunoreactive (ir) nerve terminals in the median eminence, reduction in LHRH content of the MBH and growth of novel irLHRH-containing neural processes into FC scar tissue. We have now investigated basal and secretogogue-evoked LHRH release in vitro from the preoptic area-MBH (POA-MBH) of adult male rats at 10 or 60 days after FC. Basal LHRH release rate (P less than 0.05) and total (P less than 0.01) amount released 60 days after FC were reduced when compared to control (CONT) hypothalami, but not shams. A 30 min pulse of naloxone (NAL, 1 mg/ml) stimulated greater than 2-fold relative increase in LHRH release for all groups; however, the total amount of LHRH released by FC hypothalami was less (P less than 0.05) than that of CONT, but not sham POA-MBHs. Although exposure to elevated KCl significantly increased (P less than 0.01) LHRH release for all 3 groups, the FC secretory response was less than that of both CONT (P less than 0.05) and sham (P less than 0.01) groups. In the second experiment single POA-MBH were perifused at 10 days (sham and FC) or 60 days (CONT, sham and FC) after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

The release of pituitary LH and sprouting of LH-releasing hormone (LHRH)-containing neurons after anterior hypothalamic deafferentation.

The chronology of changes in plasma luteinizing hormone (LH) and the distribution of immunoreactive neuronal processes containing LH releasing hormone (LHRH-ir) were studied in the female rat after surgical interruption of anterior neural connections of the mediobasal hypothalamus (MBH). Spontaneous LH surges on the afternoon of proestrus and LH release after estradiol benzoate (EB) followed 48 h later by progesterone (P) administration were studied in ovariectomized (OVX) rats. The maximum increase in plasma concentrations (delta maxLH) after EBP was calculated for each rat at several intervals over 140 days. Control animals given EBP at monthly intervals after OVX had comparably large delta maxLH surges during the first few months of study. However, a gradual decline in control delta maxLH followed becoming significant 3 months after the start of the experiment. In contrast, frontal cuts (FC), which interrupted anterior MBH connections, produced an abrupt decrease in delta maxLH surges after EBP to 11% of preoperative levels. However, during subsequent EBP trials, there was a gradual improvement in LH surges to about 50% of preoperative levels over 100 days. In some cases, individual improvement became equal to preoperative LH surge levels, in others there was no recovery. Examination of LHRH-ir nerve fiber growth responses after FC suggested that sprouting by these peptide-containing neuronal processes may have contributed to the functional improvements observed.

Long-term reorganization of afferents to the mediobasal hypothalamus following retrochiasmatic knife cuts. A study using horseradish peroxidase.

Retrochiasmatic knife cuts produce a series of dynamic changes across time in the luteinizing hormone-releasing hormone and catecholamine content of the mediobasal hypothalamus (MBH). We have examined the sources of afferents projecting to the mediobasal hypothalamus of female rats at 7, 60 and 90 days following retrochiasmatic frontal cut (FC) surgery using the intra-axonal retrograde transport of horseradish peroxidase (HRP) in order to better define the functional plasticity demonstrated by the MBH at these time periods after damage. Age-matched, previously unoperated, female rats served as controls. Small HRP injections placed in the ventromedial nucleus (VMN) in control animals labelled neurons within the VMN, dorsomedial nucleus (DMN) and lateral hypothalamic area (LHA). Larger injections also labelled neurons in the anterior hypothalamic area (AHA), preoptic area (POA), septal nuclei, periventricular nuclei (PVN), supraoptic nucleus (SON), zona incerta (ZI) and suprachiasmatic nucleus (Schn). Seven days after surgery, no labelled neurons could be detected rostral to the knife cut when the injection site was confined to the boundary of the glial scar. At 60 days, labelled soma were observed in LPOA, POA, AHA, PVN, SON and ZI. At 90 days only the SON contained labelled neurons rostral to the knife cut. These results suggest a dynamically changing pattern of innervation to the MBH following damage.

Electrochemical stimulation of plasma LH and hypothalamic norepinephrine concentrations at short- and long-term intervals after hypothalamic knife cuts.

Norepinephrine (NE) concentrations in several diencephalic locations were studied in female rats in conjunction with luteinizing hormone (LH) release after medial preoptic area (MPOA) stimulation at short (7 days) and longer time intervals after surgical interruption of anterior or anterolateral neural connections of mediobasal hypothalamus (MBH). Concentrations of diencephalic NE were altered in two general ways after brain surgery: (1) transient early postoperative increases in some regions which appeared unrelated to the type of surgery performed; and (2) other specific decreases in NE concentration which were related to the types of surgery performed and whether a particular ascending noradrenergic pathway was interrupted. At 180 days after surgery, these two types of change in NE concentrations were no longer present. Maximum increases in plasma LH concentrations observed after electrochemical stimulation of the MPOA at either 7 or 180 days after MBH deafferentation also varied according to: (1) the postoperative interval studied; and (2) the location of pathway interruption. Interruption of anterior MBH pathways showed only a transient (7 day interval) reduction in LH release after MPOA stimulation, whereas when both lateral and anterior pathways were severed, there was a more nearly permanent (180 day interval) disruption of LH release after stimulation. The results of these studies support the contention that anterolateral MBH neural connections may constitute a dynamic neural substrate contributing to a gradual improvement in neuroendocrine function observed after early surgical disconnections.

Changes in estrogen and progestin receptor binding resulting from retrochiasmatic knife cuts.

Retrochiasmatic frontolateral knife cuts (FLC) or sham operations (Sham) were performed with a Halasz-type knife. All animals were primed with estrogen plus 0.5 mg progesterone (P) and tested for lordosis both before and after surgery. Two weeks after the last test they received estradiol (E2) in Silastic capsules and were sacrificed 2 days later for determination of either nuclear estrogen receptors or cytosol progestin receptor binding in brain and pituitary (PIT). Rats which had received FLC showed significantly lower lordosis quotients relative to Shams, and relative to their own pre-surgery scores. Nuclear E2-receptor binding was significantly reduced in the hypothalamus (HYPO) following FLC, but not in preoptic area (POA) or PIT. No changes in cytosol P-receptor binding were observed in HYPO, POA or PIT following FLC. Our results suggest a positive correlation between the number of hypothalamic E2-receptors and the capacity to display lordosis, and emphasize the importance of anterolateral connections to the HYPO for the progesterone-induced facilitation of lordosis.

Brain catecholamine concentration during the first week of development in rats.

Neonatal brain (whole brain minus cerebral hemispheres) dopamine (DA) and norepinephrine (NE) concentrations (pg/microgram protein) were studied 30 min after an injection of L-DOPA methyl ester (50 mg/kg); haloperidol (1 mg/kg); D-amphetamine sulfate (0.5 mg/kg); saline only or no treatment. Catecholamines were assayed on the day of birth (postnatal day 1) and postnatal day 7 by high performance liquid chromatography coupled with an electrochemical detector for catecholamines (CA). When L-DOPA was administered there was a selective 7 X (postnatal day 1) or 3 X (day 7) increase in brain DA when compared to saline controls. Haloperidol pretreatment on either day prevented these increases after L-DOPA. These findings constitute biochemical evidence for selective elevation of brain DA during the first postnatal week of life after L-DOPA administration in a dosage that is also capable of enhancing the coordination required for swimming behavior.