Reduced growth hormone secretion prolongs puberty but does not delay the developmental increase in luteinizing hormone in the absence of gonadal negative feedback.

Previous studies have shown that the growth hormone (GH) axis is important for timing the later stages of puberty in female monkeys. However, it is not clear whether these growth-related signals are important for the initiation of puberty and early pubertal events. The present study, using female rhesus monkeys, used two approaches to answer this question. Experiment 1 tested the hypothesis that reduced GH secretion would blunt the rise in nocturnal LH secretion in young (17 mo; n = 7) but not older adolescent ovariectomized females (29 mo; n = 6). Reduced GH secretion was induced by treating females with the sustained release somatostatin analogue formulation, Sandostatin LAR (625 microg/kg). Morning (0900-0930 h) and evening (2200-2230 h) concentrations of bioactive LH were higher in older adolescent compared to young adolescent females. However, diurnal concentrations were not affected by the inhibition of GH secretion in either age group when compared to the placebo-treated, control condition. Experiment 2 tested the hypothesis that reduced GH secretion induced in young juvenile females would delay the initial increase in nocturnal LH secretion and subsequent early signs of puberty. In order to examine this hypothesis, puberty in control females (n = 7) was compared to those in which puberty had been experimentally arrested until a late adolescent age (29 mo) by the use of a depot GnRH analogue, Lupron (750 microg kg(-1) mo(-1); n = 7). Once the analogue treatment was discontinued, the progression of puberty was compared to a group treated in a similar fashion but made GH deficient by continuous treatment with Sandostatin LAR (n = 6). Puberty occurred as expected in control females with the initial rise in evening LH at 21 mo, menarche at 22 mo, and first ovulation at 30 mo. As expected, Lupron arrested reproductive maturation, but elevations in morning and evening LH and menarche occurred within 2 mo of the cessation of Lupron in both Lupron and Lupron-GH-suppressed females. In contrast, first ovulation was delayed significantly in the Lupron-GH-suppressed females (41 mo) compared to the Lupron-only females (36 mo). These data indicate that within this experimental model, reduced GH secretion does not perturb the early stages of puberty but supports previous observations that the GH axis is important for timing the later stages of puberty and attainment of fertility. Taken together, the data indicate that factors that reduce GH secretion may have a deleterious effect on the completion of puberty.

Tamoxifen is an estrogen antagonist on gonadotropin secretion and responsiveness of the hypothalamic-pituitary- adrenal axis in female monkeys.

The selective estrogen receptor modulator, tamoxifen, effectively slows the progression of estrogen-positive breast cancer and reduces the possibility of this cancer developing in women at high risk. Despite the widespread acceptance of tamoxifen as a therapeutic agent for this disease, its effects on other estrogen-dependent pathways, particularly on neural circuits regulating brain function and peripheral hormone secretion, are poorly understood. The present study, using previously ovariectomized rhesus monkeys, examined the effects of tamoxifen, in both the presence and absence of estradiol replacement, on the reproductive and hypo-thalamic-pituitary-adrenal (HPA) axes. In Experiment 1, monkeys randomly assigned to three groups (n = 8 each) were treated with placebo and either two doses of estradiol, two doses of tamoxifen alone, or two doses of tamoxifen plus high-dose estradiol to assess the effects on negative feedback suppression of luteinizing hormone (LH). Both doses of tamoxifen effectively antagonized the negative feedback efficacy of estradiol on LH secretion. In contrast, neither the low- or high-dose tamoxifen alone had any effect on LH secretion, as concentrations during tamoxifen treatments were indistinguishable from those during placebo. In Experiment 2, females were randomly assigned to one of four treatment groups (placebo, n = 6; estradiol, n = 5; tamoxifen only, n = 5; or tamoxifen plus estradiol, n = 6) to assess the effects on glucocorticoid negative feedback and pituitary and adrenal responsiveness to exogenous corticotropin- releasing hormone (CRH). Tamoxifen also antagonized the facilitating effects of estradiol on basal and CRH-induced ACTH and cortisol secretion. However, this antagonism produced basal and CRH-stimulated cortisol and ACTH concentrations that were lower than placebo-treated females. Interestingly, tamoxifen in the absence of estradiol produced a similar diminution in ACTH and cortisol response. These data suggest that, in the presence of estradiol, tamoxifen not only antagonized estrogenic facilitation of HPA responsivity but also actually attenuated the response compared with the placebo-treatment condition. Taken together, these data indicate that tamoxifen acts as an estrogen antagonist on the neural circuits controlling the neuroendocrine regulation of the hypothalamic-pituitary-ovarian and adrenal axes in ovariectomized macaque females.

A "pre-satiety sequence" in rats drinking sucrose solutions.

Food-deprived rats were given intermittent access or, in a replication, continuous access to a 20% sucrose solution. Both drinking and nondrinking behaviors were recorded. During the ensuing drinking bout, latency of lapping after snout apposition, and duration of lapping bouts, did not change. Approaches to the sipper tube usually eventuated in lapping, though aborted approaches increased in frequency late in the session. Drinking was interrupted by nondrinking behaviors which appeared in a characteristic rostro-caudal sequence: partial head withdrawal from the drinking aperture, then full head withdrawal, then movements of the front paws, then movement of the hind paws with full-body locomotion. All these behavioral changes occurred before there was any appreciable reduction in rate of lapping.

A robust transcutaneous electro-muscle stimulator (RTES): a multi-modality tool.

This paper introduces a transcutaneous electro-muscle stimulator design that has a wide range of output capabilities. Because of this, the unit is referred to as a robust transcutaneous electro-muscle stimulator (RTES). The RTES is a constant current stimulator that is designed to be capable of generating significant tetanic contractions from large muscle groups, such as the quadriceps. It is capable of generating complex current pulse profiles and has been tested at pulse frequencies greater than 7500 Hz. It is routinely used to generate rectangular, bi-phasic pulses in muscle-modelling studies in ranges of widths from 3 to 1000 microseconds, amplitudes from -50 to +50 mA and frequencies from 10 to 60 Hz. The design extrema on pulse width and amplitude, are 1000 microseconds and +/- 100 mA respectively. Because of the stimulator's robust output characteristics, it is suitable for many types of electro-stimulation studies including pain management, edema reduction and more.

Different effects of amphetamine on reinforced variations versus repetitions in spontaneously hypertensive rats (SHR).

The spontaneously hypertensive rat (SHR) may serve as an animal model of human attention deficit hyperactivity disorder (ADHD). We compared performances of SHRs and Wistar-Kyoto normotensive controls rats (WKY) in two experiments. When rewarded for varying sequences of responses across two manipulanda, the SHRs were more likely to vary than the WKYs. On the other hand, when rewarded for repetitions of a small number of sequences, the WKYs were more likely to learn to repeat. Both of these results confirm previous findings. Injecting 0.75 mg/kg d-amphetamine facilitated learning by SHRs to repeat the required sequences, with amphetamine-injected SHRs learning as rapidly as saline-injected, control WKYs. On the other hand, amphetamine tended to increase variability in both strains when high levels of variations were required for reward, and to decrease it in both strains when low levels of variability were required. Thus, amphetamine may have different effects on reinforced repetitions vs. reinforced variations.

Persistence of sham feeding after real-fed gastric loads in rats.

Esophagostomized rats were permitted to "real-feed" a glucose solution (Experiment 1) or milk (Experiment 2), by receiving intragastric (IG) infusions concurrent with sham feeding. This was done for the first part of the feeding session; then the IG infusions were discontinued so that subsequent ingestion was sham. When such infusions stopped after 80% of real-meal volume had been delivered, they had no measurable effect on subsequent oral ingestion: sham feeding persisted as if nothing had been delivered IG. Therefore, the onset of postingestive satiety, at least in experienced sham-feeding rats, is all-or-none or close to it: if the IG loads are even slightly short of what is required to abolish sham feeding, then they do not affect sham feeding at all. This is so even if the postingestive events occur within their normal behavioral context.

Persistence of sham feeding after intragastric meals in rats.

In rats on a stringent deprivation schedule and at reduced body weight, an intragastric load of liquid diet that equals or exceeds normal meal size has no effect at all on subsequent sham feeding of milk diet or of glucose. Removing the acute deprivation period and reversing, or preventing, severe weight reduction has no effect on this "persistence" of sham feeding: a full intragastric meal may leave sham feeding quite unaffected, even if that meal follows the previous meal at a physiological interval, in rats at normal weight. These data contrast with graded, dose-dependent effects of other manipulations by other investigators. Perhaps such effects depend on conditioned or anticipatory controls of feeding, whereas our findings apply to unconditioned controls.

Blood feeding and autogeny in the peridomestic mosquito Aedes bahamensis (Diptera: Culicidae).

Under laboratory conditions, most colony and field-collected Aedes bahamensis Berlin females developed eggs autogenously when they had access to sugar. However, significantly fewer starved females were autogenous, and they produced smaller egg clutches. Autogenous fecundity covaried with wing length, and smaller females generally failed to express autogeny. Mating had no effect on the maturation of the initial egg clutch. Most starved, nulliparous females blood fed from a restrained host. At a south Florida field site, both parous and nulliparous Ae. bahamensis were captured with a power aspirator, but concurrent sampling with dry ice-baited, light traps collected only parous females. Host-seeking females, taken either in chicken-baited traps or as they attempted to blood feed on humans, were also parous, with a single exception. Thus, at this field site, Ae. bahamensis females normally delayed blood feeding until after their first oviposition. Whether or not Ae. bahamensis females in other south Florida populations show a similar gonotrophic pattern probably will depend upon the availability of sugar sources and conditions in the mosquito's aquatic habitat that affect adult size.

Spontaneously hypertensive rats (SHR) readily learn to vary but not repeat instrumental responses.

When spontaneously hypertensive rats (SHR) and Wystar-Kyoto normotensive control rats (WKY) were rewarded in a 12-arm radial maze (Experiment 1), the SHRs varied their arm choices more, making fewer repetition errors than the WKYs. Similarly when rewards depended on variable sequences of responses on two levers in an operant chamber (Experiment 2), SHRs' sequences were more variable than those of WKYs. A requirement for response variability was then combined with a requirement to repeat selected responses in the radial maze (Experiment 3) and operant chamber (Experiment 4). WKYs learned to repeat more readily than the SHRs, whereas SHRs varied more readily. Thus, when subjects had to repeat responses, SHRs were at a disadvantage, but when variability was adaptive, SHRs excelled. The high variability of SHRs, together with their difficulty in learning to repeat, may have parallels in children diagnosed with attention deficit disorder with hyperactivity (ADDH).

Effect of body weight manipulations on sham feeding in the rat.

Rats with chronic esophageal fistulas were permitted to sham-feed a carbohydrate solution (a simplified model food) for a 40-min session each day. Body weight was elevated, then reduced again, by varying the caloric density of the liquid diet by which the rats were maintained. With 1M glucose as tastant, induction of mild obesity caused an abrupt reduction in sham meal size. Sucrose concentration-intake functions were lowered at all concentrations by mild obesity, but without change in slope. Both changes were reversed by weight reduction to around normal body weight; further weight reduction produced no further change. Therefore, some correlate of body weight biases the oral control of bout size. The bias seems to change rather abruptly between one value and another at a weight level slightly above normal.

How important is hedonism? Reasons given by college students for ending a meal.

College students (N = 64, 50, and 36 in three replications) were asked to complete the statement, "I usually stop eating a meal when ...". A number of alternatives were offered, together with an open (write-in) option. By far the most common completion was "... I feel full". The hedonic alternatives, "... the food stops tasting good" (first study) or "the food tastes less good" (first replication) were chosen by very few of the subjects, though explicitly presented as alternatives. In a second replication, subjects rank-ordered in importance the various reasons for ending a meal; not all subjects ranked the hedonic alternative at all, and most of those who did ranked it low in importance. Though hedonic shifts during a meal have been repeatedly shown to occur, these data suggest that they are of little salience, and perhaps of little importance, as factors in meal termination.

Preparation and maintenance of chronic esophagostomized rats: an update.

We report significant improvements in our procedures for preparing and maintaining rats with esophageal fistulas and gastric cannulas. The most important of these are 1) a new cannula assembly, 2) a two-stage surgical procedure, 3) a modified diet, and 4) a less stringent maintenance regimen.

All-or-none suppression of glucose sham feeding by an intragastric mixed meal in rats.

Rats were permitted to sham feed a 1 M glucose solution after varying delays (0-40 min) following the intragastric (IG) infusion of a large, nutritionally adequate meal. (a) The meal affected sham feeding in an all-or-none way. After such a meal, sham feeding was either suppressed almost entirely, or it was not suppressed at all as compared with a no-meal control condition. (b) When it occurred, the suppression was short-lived: As little as a 20-min delay after the meal could suffice to change its suppressant effect from "all" to "none." This implies in turn that the much longer suppression found under other conditions is not a product of systemic inhibition on readiness to ingest. (c) The duration of the suppression appeared to decrease with successive exposures to the experimental conditions. After several such exposures, some rats showed no postprandial suppression at all, even immediately after the IG meal.

Resistance of congenitally immunodeficient gnotobiotic mice to vaginal candidiasis.

Congenitally immunodeficient beige, athymic, and beige athymic mice whose orogastric mucosal tissues were chronically colonized and infected with a pure culture of Candida albicans were found to be resistant to naturally occurring vulvovaginal candidiasis.

Functional recovery of the gustatory system after sodium deprivation during development: how much sodium and where.

Restriction of maternal dietary sodium beginning on or before embryonic day 8 and continued thereafter results in reduced taste responses of the chorda tympani nerve to NaCl in the offspring. The effects of deprivation, however, are reversible. A single ingestive bout of 30 ml isotonic NaCl was sufficient to restore normal sodium taste, and the restorative effects of the single exposure apparently persisted throughout multiple generations of taste receptor cells. Furthermore, the recovery apparently did not depend on direct receptor cell-stimulus interactions. Rats permitted to drink 30 ml of isotonic NaCl, but not allowed to retain it, did not recover normal sodium taste responses, suggesting that factors other than taste stimulation are important in the restorative effects of sodium.

Facultative blood-feeding in the crabhole mosquito, Deinocerites cancer.

1. Most of the female crabhole mosquitoes Deinocerites cancer Theobald entering bait traps had undeveloped ovaries. 2. Nearly half of the D. cancer females that were captured in bait traps, but denied blood, were gravid following a 1 week holding period; they developed relatively small egg clutches autogenously (mean = 7.4 eggs per gravid female). 3. Although both parous and nulliparous D. cancer females were captured exiting from crabholes, only parous females were attracted to and collected in bait traps. 4. Much larger egg clutches (mean = 41.8 eggs per female) were produced anautogenously by mosquitoes that blood-fed on chickens. 5. All D. cancer females from field collected pupae developed eggs autogenously when allowed to mate and sugar feed in the laboratory. These mosquitoes produced an initial egg clutch with a mean size equivalent to that found in blood-fed, parous mosquitoes from bait traps. 6. In the field, mating and sugar feeding rather than blood-feeding seem to stimulate production of the initial egg clutch. 7. D. cancer blood-feeding appears to be delayed until after the first egg clutch has been laid; some parous crabhole mosquitoes are facultative blood feeders and can produce an egg clutch either with or without a blood meal.

Orosensory suppression of saccharin drinking in rat: the response, not the taste.

Hungry rats drink saccharin solutions with avidity, but the ingestion is self-limited: rate of lapping slows down progressively. Since postingestive changes do not produce this suppression, it must depend on a feedback signal generated by lapping the fluid. We show that the suppression depends on the number of laps emitted, not on the taste of the fluid; a given number of laps early in the session produces the same suppression later in the session, whether those early laps are accompanied by a moderate saccharin taste, a weak taste, or no sweet taste at all. Therefore, the feedback signal is provided by the act of lapping; taste does not contribute to it. Yet taste does influence amount ingested. Perhaps it provides a feed-forward signal, that in turn sets the amount of feedback required to end the bout.

Aedes bahamensis: its invasion of south Florida and association with Aedes aegypti.

The exotic mosquito, Aedes bahamensis, is now well-established in south Florida, where it is widely distributed throughout Dade and southern Broward Counties in both urban and rural areas east of the Everglades. When discarded automobile tires were sampled in areas near human habitation, larvae and pupae of Ae. bahamensis were frequently found in association with immature Ae. aegypti. Elsewhere, however, Ae. bahamensis generally occurred in the absence of Ae. aegypti. The persistence of Ae. bahamensis populations at specific sites was documented in egg collections from ovitraps and in larval samples from the water retained in discarded tires.

Adjustment to intermittent access in rats drinking saccharin: II. Adjustment of lapping rate.

Hungary rats were permitted to drink saccharin under conditions in which (a) the drinking spout was available continuously, or (b) it was withdrawn during alternate 30-sec periods. Rats adjust to such constraint by increasing their integrated lap rate (laps/min). We show that one way in which they do this is to lap at a higher rate within bursts of lapping. This faster lapping is not an artifact of forced interruptions and resumptions. It cannot only be maintained over a drinking session, but also initiated midway through the session if restricted access is imposed then. Therefore, the period of the lapping cycle can be adjusted, within limits, in response to situational constraints on access to the fluid.