Multiple processes underlie benzodiazepine-mediated increases in the consumption of accepted and avoided stimuli.

Hyperphagia is a reported side effect of anxiolytic benzodiazepines such as chlordiazepoxide (CDP). Prior research has focused primarily on the ingestive responses to sweet or solid foods. We examined CDP effects on licking for normally accepted and avoided taste solutions across a range of concentrations. The effect of CDP (10 mg/kg) versus saline on the licking patterns of water-restricted rats for water and 3 concentrations of sucrose, saccharin, NaCl, monosodium glutamate (MSG), citric acid, and quinine (Q-HCl) solutions was evaluated during 1 h tests. CDP increased meal size for all tastants except citric acid. Analysis of licking microstructure revealed 3 dissociable effects of CDP. CDP affected oromotor coordination as indicated by a uniform increase in the modal interlick interval for all stimuli. CDP increased meal size as indicated by shorter pauses during consumption of water, MSG, and weaker saccharin concentrations, and by fewer long interlick intervals (250-2000 ms) for normally avoided tastants. CDP also increased meal size by increasing burst size, burst duration, and the initial rate of licking for most solutions, suggesting increased hedonic taste evaluation. CDP did not affect variables associated with postingestive feedback such as meal duration or number of bursts, and the results also suggest that CDP did not enhance the perceived taste intensity. We hypothesize that the reduction of pause duration is consistent with an increased motivation to sample the stimulus that synergizes with changes in taste-mediated responsiveness to some but not all stimuli to yield increases in the consumption of both normally accepted and avoided taste stimuli.

Licking for taste solutions by potassium-deprived rats: specificity and mechanisms.

There has been little work on the specificity and mechanisms underlying the appetite of potassium (K(+)) deprived rats, and there are conflicting results. To investigate the contribution of oral factors to changes in intake induced by K(+) deficiency, we conducted two experiments using 20-s "brief access" tests. In Experiment 1, K(+)-deprived rats licked less for water than did replete rats. After adjusting for this difference, K(+)-deprived rats exhibited increased licking for 100 mM CaCl(2), 100 mM MgCl(2), and 100 mM FeCl(2) compared with K(+)-replete rats. In Experiment 2, which used larger rats, the K(+)-deprived and replete groups licked equally for water, 500 mM Na.Gluconate, 350 mM KCl, 500 mM KHCO(3), and 1 mM quinine.HCl, but the K(+)-deprived rats licked more for 500 mM KCl, 500 mM CsCl, and 500 mM NaCl than did the replete rats. Licking was unaffected by addition to NaCl of 200 muM amiloride, an epithelial Na(+) channel (ENaC) blocker, or 100 muM ruthenium red, a vanilloid receptor 1 (VR-1) antagonist, or by addition to KCl of 50 muM 4-aminopyridine, a K(+) channel blocker. These findings suggest that K(+)-deprivation produces a non-specific appetite that is guided by oral factors. We found no evidence that this response was mediated by ENaC, VR-1, or K(+) channels in taste receptor cells.

C57BL/6J and DBA/2J mice vary in lick rate and ingestive microstructure.

Fluid licking in mice is an example of a rhythmic behavior thought to be under the control of a central pattern generator. Inbred strains of mice have been shown to differ in mean or modal interlick interval (ILI) duration, suggesting a genetic-based variation. We investigated water licking in the commonly used inbred strains C57BL/6J (B6) and DBA/2J (D2), using a commercially available contact lickometer. Results from 20-min test sessions indicated that D2 mice lick at a faster rate than B6 mice (10.6 licks/s vs. 8.5 licks/s), based on analysis of the distribution of short-duration ILIs (50-160 ms). This strain difference was independent of sex, extent of water deprivation or total number of licks. D2 mice also displayed a faster lick rate when the strains were tested with a series of brief (5 s) trials. However, when ingestion over the entire 20-min session was analyzed, it was evident that D2 mice had an overall slower rate of ingestion than B6 mice. This was because of the tendency for D2 mice to have more very long pauses (>30 s) between sequences of licking bursts. Overall, it appeared that D2 mice licked more efficiently, ingesting more rapidly during excursions to the spout that were fewer and farther between.

Parametric analysis of gastric distension responses in the parabrachial nucleus.

The parabrachial nucleus (PBN) is regarded as an important locus for the processing and integration of sensory inputs from oral, gastrointestinal, and postabsorptive receptor sites and is thus thought to play an important role in regulating food intake. Gastric distension is an important satiation cue; however, such responses have been qualitatively characterized only over a limited area of the PBN. To more fully characterize gastric distension responses throughout the PBN, the responses of single units to gastric distension were tested using computer-controlled balloon inflation (3-18 ml air) in pentobarbital sodium- and/or urethan-anesthetized male rats. Distension-responsive neurons were indeed distributed throughout the nucleus from rostral areas typically considered to be visceral to more caudal areas associated with gustatory function, providing further anatomical support for the hypothesis that the PBN integrates taste and visceral signals that control feeding. Most PBN neurons had thresholds of 6 ml or less, similar to vagal afferent fibers. However, in contrast to the periphery, there were both excitatory and inhibitory responses. Increases in volume were associated with two distinct effects. First, as volume increased, the response rate increased; second, the duration of the response increased. In fact, in a subset of cells, responses to gastric distension lasted well beyond the stimulation period, particularly at larger volumes. Prolonged gastric distension responses are not common in the periphery and may constitute a central mechanism that contributes to satiation processes.

Integration of gastric distension and gustatory responses in the parabrachial nucleus.

Palatable gustatory stimuli promote feeding, whereas gastric distension generally inhibits this behavior. We explored a neural basis for integration of these opposing sensory signals by evaluating the effect of gastric distension on gustatory responses in the parabrachial nucleus (PBN) of anesthetized rats. Sixteen percent of 92 taste cells were coactivated; they responded to independent taste or gastric distension stimulus application. Modulation of taste responses by distension was more prevalent; taste responses declined 37% in response to distension in 25% of the cells and increased by 46% in 10% of cells. Across the whole population, however, the suppressive effect of distension on taste responses was small (6%). The incidence of modulation did not vary as a simple hedonic function of gustatory sensitivity, i.e., similar proportions of sucrose-, citric-acid-, and QHCl-best, but not NaCl-best, neurons were modulated by gastric distension. Coactivated, modulated, and nonmodulated gustatory-responsive cells were intermingled in the gustatory zone of the caudal PBN. The suppression of PBN taste responses by visceral stimulation may reflect a mechanism for satiation and further implicates the PBN in the control of ingestive function.

Dissociation of licking and volume intake controls in rats ingesting glucose and maltodextrin.

The volume of fluid that rats acquire with each lick was systematically varied across short-term tests with 12.5% glucose (Experiment 1) or 12.5% maltodextrin (Experiment 2). For glucose, rats increased the number of licks emitted as lick volume was reduced such that meal size remained remarkably stable across all (8, 4, and 2 microl) but the smallest (1 microl) lick volume conditions tested. Rats similarly compensated for lick volume reduction (8 to 4 microl) with maltodextrin by approximately doubling the number of licks emitted. Meal duration and a number of lick-microstructural parameters (initial ingestion rate, mean burst duration, terminal lick and ingestion rates, and burst duration) were not correlated with the intake outcome insofar as they varied significantly across conditions over which intake remained stable. Thus, in response to lick volume manipulation, rats demonstrated an impressive degree of behavioral flexibility in what may be regarded as a defense of meal size.

Effect of hepatic glucose infusion on glucose intake and licking microstructure in deprived and nondeprived rats.

The effects of hepatic-portal glucose or saline infusions on intake and the temporal distribution of licking (lick microstructure) were evaluated in nondeprived and in 20.5-h food-deprived rats. Rats received portal infusions of isotonic glucose or saline (0.1 ml/min) for 2 h before and then throughout a 90-min period of access to a spout that delivered 12.5% glucose. Overall, a significant treatment-related intake suppression was obtained in nondeprived but not in deprived groups. For both groups, however, there was a significant positive linear relationship between the amount individual rats consumed under the saline (baseline) infusion condition and the extent to which portal glucose infusion suppressed intake. The linear fit for the deprived group was similar in slope, but right shifted, relative to the best fit for the nondeprived group. The individual-subject and group differences in response to portal glucose infusion are discussed in relation to the inconsistent literature on this treatment's short-term intake effects. We focused analysis of the licking pattern on those rats for which a prominent portal glucose infusion effect was obtained (i.e., nondeprived rats with higher than average baseline intakes). Features of the lick pattern associated with taste evaluation (1st min lick rate; lick burst duration) were not significantly affected by portal glucose infusion. Rather, the minute-by-minute rate of ingestion under glucose infusion declined more rapidly than under baseline tests, indicating that portal glucose infusion enhanced the inhibitory influence of the accumulating postingestive load.

Fringe-orientation estimation by use of a Gaussian gradient filter and neighboring-direction averaging.

We analyze the effect of image noise on the estimation of fringe orientation in principle and interpret the application of a texture-analysis technique to the problem of estimating fringe orientation in interferograms. The gradient of a Gaussian filter and neighboring-direction averaging are shown to meet the requirements of fringe-orientation estimation by reduction of the effects of low-frequency background and contrast variances as well as high-frequency random image noise. The technique also improves inaccurate orientation estimation at low-modulation points, such as fringe centers and broken fringes. Experiments demonstrate that the scales of the Gaussian gradient filter and the direction averaging should be chosen according to the fringe spacings of the interferograms.

d-fenfluramine anorexia: dissociation of ingestion rate, meal duration, and meal size effects.

In the present study, we ask whether the suppressive effect of d-fenfluramine (d-FEN) on short-term intake can be better explained in terms of a primary action on particular behavioral parameters (e.g., ingestion rate or meal duration), as proposed by several investigators, or in terms of a primary effect on an intake "target" that can be achieved via diverse behavioral strategies. We applied two specialized intake testing paradigms that constrain the behavioral structure of the rat's meal in different ways, and determined whether or not the meal-size result varied in turn. (1) In the intraoral intake test, the rate of ingestion was clamped by the rate (1.0 ml/min) at which the test stimulus (12.5% glucose) was intraorally delivered. A d-FEN (3 mg/kg) suppression of intraoral intake was obtained demonstrating that ingestion rate adjustment is not necessary for the anorexic effect. In addition, for both d-FEN and vehicle conditions, comparable amounts were consumed when the intraoral intake test was either continuous or interrupted for 10 min beginning 6 min after test onset. For d-FEN, the increase in meal duration (mean = 11.98 min) required to compensate for the imposed interruption indicates that the drug does not specify an absolute limit for meal duration. (2) In the drop size-controlled spout-licking test, the volume of 12.5% glucose delivered for each lick was fixed at either 8 or 4 microliters. There was an overall reduction in intake with d-FEN (0.75 mg/kg), but as under vehicle injection conditions, the number of licks emitted approximately doubled when lick volume was halved. As a result, meal size was unaffected by the drop size manipulation. The drop size manipulation affected several other behavioral parameters under respective d-FEN and vehicle injection conditions, including: average rate of ingestion (ml/min), initial ingestion rate, and ingestion duration (meal duration minus pause time). The two experiments together demonstrate that the anorexic effect of d-FEN does not depend on adjustment of any particular behavioral parameter. The results suggest, rather, that given doses of d-FEN establish a particular degree of intake suppression that the rat defends via diverse behavioral strategies.

Intake suppression after hepatic portal glucose infusion: all-or-none effect and its temporal threshold.

The effects of hepatic portal infusions of isotonic glucose on glucose intake (3.2%) were evaluated with use of the intraoral intake test, which, unlike traditional tests, permits delivery of portal infusions in explicit temporal relationship to intake onset in nondeprived rats. Continuous or discontinuous portal infusions (0.1 ml/min) of isotonic glucose or saline were initiated 0, 30, 60, or 120 min before meal onset. Jugular infusions of isotonic saline or glucose and portal infusions of isotonic saline were without effect. For all effective portal glucose infusions, intake was suppressed by approximately 30% of baseline values. Because the duration (and quantity) of effective portal glucose infusions varied by a factor of 10, we conclude that intraoral intake suppression under these conditions is all or none in nature. Whether an intake suppression was obtained depended more on when the infusion was delivered than on how much was infused. Thus 1.5 ml of isotonic glucose infused between 60 and 45 min before the intake test was effective, whereas 3.0 ml infused for the 30 min before intake was without effect. These results suggest that the liver participates in the control of future intake but not in the termination of an ongoing meal. The temporal requirement for intake suppression should be considered in analyses of the metabolic, hormonal, and/or neural mechanisms that underlie the liver's contribution to intake control.

Growth hormone-releasing hormone mediates feeding-specific feedback to the suprachiasmatic circadian clock.

Growth hormone-releasing hormone (GHRH) is known to stimulate food intake in a circadian phase-dependent manner in rats. The suprachiasmatic nucleus (SCN) is an important site of action for this effect. In light of the central role played by the SCN in the control of circadian rhythms, together with the phase-dependent nature of GHRH-induced feeding, we sought to determine the possible involvement of SCN GHRH activity in the regulation of circadian rhythmicity. Two studies were conducted using hamsters as subjects. Study one replicated the daytime feeding-stimulatory effects of GHRH in hamsters, thereby validating its appetitive effects in this species. Study two showed that, in free-running hamsters, intra-SCN microinjections of GHRH produced phase advances when injected during the subjective day while having little effect during the subjective night. The GHRH phase-response curve was found to resemble that observed for nonphotic influences on the clock. It is suggested that GHRH input to the SCN is a neural representation of a nonphotic influence (perhaps feeding specific) on the clock.

Beam-propagation method applied to the deflection of a laser beam across a hot plate subject to jet impingement.

We describe an application of the beam-propagation method of Fleck et al. [Appl. Phys. 10, 129-160 (1976)], whereby we consider a laser beam propagating initially parallel to a hot plate subject to jet impingement; we also compute the intensity profile of the beam as it emerges from the boundary layer. A comparison with a calculation based on ray tracing illustrates the significant role of wave effects (as treated by the beam-propagation method) in this case. We describe a method for measuring the rate of heat transfer q????#x0307???? in the viscous sublayer that is applicable in the ray-tracing limit but that cannot be utilized here (other than to provide an upper limit to q????#x0307????) because of the substantial wave effects.

Individual differences in the feeding effects of amphetamine: role of nucleus accumbens dopamine and circadian factors.

Evidence indicates that amphetamine (AMP) affects feeding in a baseline-dependent fashion and that the nucleus accumbens (Acc) is an important site of action for AMP's effects on feeding. Experiment 1 examined the contribution of Acc-dopamine (DA) mechanisms to the baseline-dependent feeding effects of a 0.125 mg/kg dose of AMP using intra-Acc administrations of cis-flupenthixol (FLU). Results showed that there was an inverse relation to AMP, such that AMP stimulated feeding in animals with high baseline intake. Intra-Ace FLU administration reversed the stimulatory but not the inhibitory effect of AMP. Further, intra-Acc FLU attenuated baseline feeding in high but not low baseline feeders. Experiment 2 sought to determine whether AMP would affect feeding in a baseline-dependent manner when administered in the dark photoperiod of the rat circadian cycle, when rats do most of their feeding. To this end, rats were administered three doses (0.05,0.01, and 0.25 mg/kg) of AMP in the dark photoperiod and the intake of sugar monitored. Results showed that in low baseline feeders, AMP stimulated intake at lowest dose and had no effect at higher doses. In high baseline feeders, AMP inhibited intake in a dose-dependent manner. Taken together, these results further establish that AMP affects feeding in a baseline-dependent fashion. Moreover, the similar effects of AMP across the light and dark photoperiods suggest that a straightforward rate-dependency interpretation is not adequate. Finally, it is speculated that Acc-DAergic activity may play a role in the observed differences in baseline intake levels and in the response to AMP.

Three-dimensional displacement measurement by a holospeckle interferometry method.

The three-dimensional displacement of a structure may be measured by holographic interferometry and speckle interferometry. Under the general heading of holographic interferometry a number of distinct techniques are possible. These include the zero-fringe method, which uses three separate holographic plates, the fringe-localization method, and the fringe-counting method, all of which require a complicated recording and analysis system and high stability. These requirements make the techniques unsuitable for use in most industrial settings. In this paper we present a holospeckle interferometry method that couples objective speckle and reflective holographic interferometry and that is capable of obtaining the three-dimensional displacement of an opaque object with good visibility and resolution by a single holographic plate. Being inexpensive and portable, the recording and analysis system can readily be adapted to industrial use.

Effect of nalidixic acid on the growth of deoxyribonucleic acid bacteriophages.

The effect of nalidixic acid on the growth of various deoxyribonucleic acid (DNA) bacteriophages has been investigated by one-step growth experiments. The Escherichia coli bacteriophages T5, lambda, T7 and phiR are strongly inhibited by nalidixic acid, whereas T4 and T2 are only partially inhibited. The Bacillus subtilis bacteriophages SP82, SP50, and phi29 are relatively unaffected by nalidixic acid. There is no correlation between those bacteriophages which can grow in the presence of nalidixic acid and the presence of an unusual base in the phage DNA.

Acridine sensitivity of bacteriophage T2H in Escherichia coli.

Normally acridine-sensitive, Escherichia coli-T2H complexes are rendered acridine-resistant if the infecting bacteriophage mutant is either pr or q. If these pr or q mutants are treated to produce sensitive revertants, one obtains a mutation at any of several dye-sensitizing (ds) sites in the early enzyme region of the T2 map. The ds mutants are nonspecific suppressors because they reduce the resistance of complexes containing either pr or q to proflavine. The ds mutants are not identical in action, since some make pr or q sensitive to proflavine and quinacrine, and others, to proflavine alone. Two ds mutants have r to r(+) mutation patterns which differ, depending upon whether or not the ds is coupled with r7 (an rII mutant). The mutation patterns of r(+) to r are the same for both ds mutants and for wild type. We suggest that dye sensitization may consist of alterations of early enzymes so as to produce slightly different forms of deoxyribonucleic acid which are in turn dyesensitive.