Biomedical subjects

M D Holder

Publications and source records attributed to M D Holder.

At least 19 recordsLinked to original sources

PubMed1998

Enhanced preference for a protein-containing diet in response to dietary protein restriction.

Rats were maintained for 10 days on either a protein-free or a nutritionally complete maintenance diet, and they were also given access to protein-rich and carbohydrate-rich test diets during separate daily 2-h test sessions. In Experiment 1, rats maintained on the protein-free diet gradually and selectively increased their intake of the protein test diet, and eventually derived 16% of their daily energy intake from the protein test diet. Rats maintained on a nutritionally complete diet ate similar amounts of the two test diets even when their total caloric intake was matched to that of rats maintained on the protein-free diet. In Experiment 2, rats that developed a preference for the protein test diet while maintained on a protein-free diet were given Purina Chow for 25 days to allow them to recover from their protein deficiency. When these rats were later returned to the protein-free diet for 10 days, their preference for the protein test diet was immediate and sustained. However, if they were maintained on the nutritionally complete diet after the 25-day recovery period, they initially preferred the protein test diet, but this preference diminished over days. Results of these studies are consistent with other findings showing that rats can learn to compensate for macronutrient deficiencies by using oral-sensory cues. In particular, the rats' diet selection was consistent with their having learned a preference for the cues paired with dietary protein.

Animal Nutritional Physiological Phenomena↗

PubMed1997

Food cravings, endogenous opioid peptides, and food intake: a review.

Extensive research indicates a strong relationship between endogenous opioid peptides (EOPs) and food intake. In the present paper, we propose that food cravings act as an intervening variable in this opioid-ingestion link. Specifically, we argue that altered EOP activity may elicit food cravings which in turn may influence food consumption. Correlational support for this opioidergic theory of food cravings is provided by examining various clinical conditions (e.g. pregnancy, menstruation, bulimia, stress, depression) which are associated with altered EOP levels, intensified food cravings, and increased food intake.

Alcoholism↗

PubMed1997

Antinociceptive effects of palatable sweet ingesta on human responsivity to pressure pain.

Palatable sweet ingestion produces a morphine-like analgesia in both rats and human infants (2-5). To determine whether palatable sweet ingesta induces antinociception in human adults, 60 university students (30 men, 30 women) were exposed to a pressure algometer both before and after consuming either a sweet soft drink, filtered tap water, or nothing (Experiment 1). Pain responsivity was assessed with four pain measures: threshold, tolerance, and visual analogue scale (VAS) ratings of intensity and unpleasantness. Results showed that women who consumed either soft drink or water reported increased pain tolerance and VAS ratings at posttreatment compared with those receiving nothing. However, differences between groups were not found for men. Moreover, compared to men, women reported lower pain thresholds and tolerances and rated the pain as more intense. In Experiment 2, 40 women consumed either nothing or foods that they rated previously as palatable (chocolate-chip cookies), unpalatable (black olives), or neutral (rice cakes). Women who consumed the palatable sweet food showed increased pain tolerance compared with those receiving the unpalatable food, the neutral food, or nothing. These data constitute the first demonstration that "palatability-induced antinociception" (PIA) can occur in human adults.

Adolescent↗

PubMed1994

Effects of time-restricted access to protein and of oral-sensory cues on protein selection.

The effects on protein consumption of restricting access to protein and of varying the oral-sensory properties of protein diets were measured. During the initial phase of the study, rats were maintained on a self-selection diet in which three different macronutrient sources (carbohydrate, fat, and either soy-based or casein-based protein diets) were continuously available. For the remaining 9 days of the study, half of the rats were protein deprived for 23 h each day and the other half continued to receive the same protein diet during this 23-h period. The remaining 1 h of each day was a test period in which all rats had access to a protein diet that was either the same as or different from the one they had received in the initial phase. Compared to the nonrestricted rats, the protein-restricted rats consumed diet during 1-h test periods. For the nonrestricted rats, those that received diet during 1-h test periods. For the nonrestricted rats, those that received a different protein diet during the 1-h test periods consumed 60% more of the protein diet than did those that received the same protein diet. These results indicate that increases in protein consumption following protein deprivation can be attributed, at least in part, to the oral-sensory properties of diets and not necessarily to a specific protein appetite.

Animals↗

PubMed1993

Responses to anomalous gestural sequences by a language-trained dolphin: evidence for processing of semantic relations and syntactic information.

This study examined the responses of a bottlenosed dolphin (Tursiops truncatus) to "normal" (semantically and syntactically correct) sequences of gestures and to anomalous sequences given within an artificial gestural language highly familiar to the animal. Anomalous sequences violated the semantic rules or syntactic constraints of the language. The dolphin discriminated anomalous from normal sequences in that rejections (refusals to respond) occurred to some anomalous sequences but never to normal sequences. Rejections rarely occurred, however, if the anomalous sequence contained a subset of gestures that would comprise a normal unit if joined together. Such units were typically perceived by the dolphin and responded to even if they consisted of gestures that were not sequentially adjacent. All semantic elements of a sequence were processed by the dolphin in relation to other elements before the dolphin organized its final response. The results show the importance of both semantic properties and semantic relations of the referents of the gestures and of syntactic (ordering) constraints in the dolphin's interpretations of the anomalies.

Animal Communication↗

PubMed1991

Conditioned preferences for the taste and odor components of flavors: blocking but not overshadowing.

Sprague-Dawley rats were given two water bottles. One bottle contained sucrose and the other did not. Distinctive odors and/or tastes were paired with sucrose or plain water solutions. Preferences for the odor and taste were then measured under iso-caloric conditions when the rats were and were not food deprived. The rats preferred the odor or taste that had previously been paired with sucrose. The strength of this preference increased when the rats were food deprived suggesting that the effect was calorie mediated. The development of a preference to the odor or taste was not affected by the addition of a taste or odor; there was no evidence of overshadowing. Conditioned taste and odor preferences were partially blocked by prior pairing of the odor or taste with sucrose. The absence of overshadowing, but not the presence of blocking, was predicted by a theory of associative learning which treats odors as conditioned stimuli, tastes as unconditioned stimuli and ingestional consequences (e.g. calories or illness) as a new category referred to as feedback.

Animals↗

PubMed1990

Role of prefeedings, plasma amino acid ratios and brain serotonin levels in carbohydrate and protein selection.

The relationship between carbohydrate and protein consumption and brain serotonin levels was investigated using Sprague-Dawley rats trained to press two levers. Each response on one lever was followed by a carbohydrate-rich 45-mg food pellet and each response on another lever was followed by a 45-mg pellet relatively high in protein. Access to the carbohydrate pellets immediately prior to the daily session depressed the number of carbohydrate pellets consumed but had little effect on the number of protein pellets consumed. Prior access to standard rat chow, which is relatively high in protein, had the opposite effect. Prior access to carbohydrates in solution did not affect pellet consumption. Plasma amino acid levels and brain serotonin levels were altered by intraperitoneal injections of insulin (2.4 U/kg) and tryptophan (40 mg/kg), but consumption of carbohydrate pellets relative to protein was not changed by these injections. Saline and glucose injections did not change relative consumption either. The results emphasize the importance of oral-sensory cues in food intake and selection but are not supportive of a major role for serotonin.

Amino Acids↗

PubMed1990

The conditioned stimulus-unconditioned stimulus-feedback feeding sequence: reply to Ellins, von Kluge, and Cramer (1990).

Taste-potentiated noise aversions have been demonstrated in rats (Ellins, Cramer, & Whitmore, 1985; Ellins & von Kluge, 1987; Holder, Bermudez-Rattoni, & Garcia, 1988). However, these aversions are apparently less readily established than taste-potentiated odor aversions suggesting that all exteroceptive stimuli are not equally well potentiated by taste (Holder et al., 1988). Despite the claims of Ellins, von Kluge, and Cramer (1990), we replicated their findings and see no inconsistency between our findings and theirs. Both sets of results are explained by a common theory of conditioning (Garcia, 1989; Garcia & Holder, 1985).

Animals↗

PubMed1989

Behavioral assessment of the toxicity of aspartame.

Six experiments with rats assessed the toxicity of aspartame with behavioral measures. The first three experiments used a conditioned taste aversion procedure since taste aversions are typically observed after a taste is followed by a toxin. Thirty min after thirsty rats drank a sweet solution they were intraperitoneally injected (Experiment 1) or intragastrically intubated (Experiment 2) with saline or 176, 352, or 704 mg/kg of aspartame. Relative to rats given saline, rats injected with 704 and 352 mg/kg aspartame showed strong and mild aversions, respectively. Rats injected with 176 mg/kg of aspartame or intubated with any dose of aspartame did not show taste aversions. In Experiment 3, rats voluntarily consumed an aspartame solution sweetened with saccharin for 7 hr each day. Consumption of the taste paired with aspartame was not reduced. When 352 mg/kg aspartame was injected (Experiment 4), but not when intubated (Experiment 5), 5 min prior to access to a running wheel, running was reduced. Wheel running was not affected by the voluntary consumption of aspartame (Experiment 6). The route of administration effect (intraperitoneal vs. intragastric) on behavior corresponded with the amino acid levels in blood plasma (Experiment 7). Aspartate, phenylalanine, tyrosine and glutamate levels increased more after the injection, than the intubation, of aspartame (176 mg/kg). Overall, the results suggest that aspartame may have adverse effects when intraperitoneally injected but not when the route of administration is oral.

Amino Acids↗

PubMed1989

Conditioned taste aversions are not readily disrupted by external excitation.

Thirsty male rats were given saccharin water followed by delayed illness. During the delay, some of the rats were exposed to events designed to stimulate their external systems (i.e., the system that processes external events such as auditory and tactile stimulation). Access to females, mild footshocks, and pain from hypertonic saline injections did not interfere with either the acquisition or extinction of a taste aversion. In fact, when administered intraperitoneally, the hypertonic saline slightly increased the strength of the aversion. Exposure to heat, which changed both skin temperature and core temperature, slightly attenuated the formation of the aversion. Overall, these results emphasize the independence of the internal system (i.e., the system that deals with internal events such as taste, illness, and core temperature) and the external system. Furthermore, the associating of events related to the internal system is not readily interfered with by events related to the external system.

Animals↗

PubMed1988

Partial recovery of gustatory function after neural tissue transplantation to the lesioned gustatory neocortex.

The ability of homotypic cortical tissue grafts to induce recovery of function after a gustatory neocortex (GN) lesion was studied using the conditioned taste aversion (CTA) paradigm. On acquisition day, 26 GN-lesioned and 8 sham-lesioned rats were presented with a saccharin solution, followed by an injection of the illness-inducing agent lithium chloride (LiCl). On the test day, 2 days later, saccharin was presented again. The GN-lesioned rats showed significantly less aversion to saccharin on the test day, indicating that the lesion impaired their ability to form taste-illness association. Nine of the lesioned rats were then bilaterally transplanted with fetal GN tissue. Nine weeks after the transplantation, the rats were presented with a LiCl solution, which served as both a tastant and an illness-inducing agent. An NaCl solution, which tasted very similar to the LiCl solution, was used to test the CTA to salt 3 days later. The nontransplanted rats consumed significantly more LiCl than the transplanted and sham-operated rats on the acquisition day, but both transplanted and nontransplanted rats consumed more NaCl than sham-operated rats on the test day. Nissl and Golgi stainings showed numerous somata and extensive arborization of neurons within the grafts. The results indicate that fetal GN grafts can restore the ability to integrate gustatory and visceral inputs but not to form long-lasting taste-illness associations.

Animals↗

PubMed1988

Chronic sweet intake lowers pain thresholds without changing brain mu- or delta-opiate receptors.

Sprague-Dawley rats drank sweetened (3% dextrose + 0.144% saccharin, w/v) or unflavored water for 18 days and subsequent pain reactivity was assessed using a hot plate. Compared to the rats that consumed unflavored water, the rats that consumed sweet water responded more quickly on the hot plate indicating that their threshold for pain was lowered. Another group of rats given identical exposure to the fluids had their brains prepared for measuring opiate receptor binding using the delta-receptor ligand [3H]D-Ala-D-Leu-enkephalin ([3H]DADLE) and the mu-receptor selective ligand [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol ([ 3H]DAGO). Binding of these opiates to mu- and delta-receptors in the cerebral cortex, striatum, hippocampus, hypothalamus, brain stem, and remaining brain regions was the same for the rats that drank sweet fluids and those that drank unflavored water. These findings suggest that drinking sweet fluids lowers pain thresholds but does not alter mu- and delta-receptors.

Animals↗

PubMed1988

Responsivity to pain in rats changed by the ingestion of flavored water.

Sprague-Dawley male rats drank flavored water and subsequent pain responsivity was assessed using a hot plate first after isotonic saline and later after either 2.75 (Experiment 1) or 2.5 (Experiment 2) mg/kg of morphine hydrochloride was injected. A 48-h exposure to any one of several different flavors resulted in a reduction of the analgesic effects of morphine as shown by an attenuation of the increased latency to paw lick caused by the morphine. This effect was independent of the amount consumed. A 26-h exposure to a flavor decreased pain reactivity before and after morphine as shown by an overall increase in latency to paw lick. This effect was not influenced by whether the normally preferred flavor was made aversive by a previous pairing with lithium chloride-induced illness. These findings are consistent with the idea that many flavors, independently of palatability and amount consumed, increase the release and utilization of endogenous opioids.

Animals↗

PubMed1988

Taste-potentiated noise-illness associations.

In five experiments we attempted to establish aversions to a noise presented each time thirsty rats licked a water source. Using an apparatus and a procedure similar to those of previous studies which reported noise-illness associations, weak taste-potentiated noise-illness associations were found (Experiment 1). However, when the apparatus and procedure were varied, noise-illness associations were not observed (Experiments 3, 4, and 5). The noise used in all of these failures was readily associated with shock (Experiment 2), which indicates that this noise was salient to the rats and could be associated with an aversive event. These failures to find noise-illness associations occurred despite the fact that the conditions were chosen to maximize the likelihood of observing these associations. Taste-illness associations always developed normally. The results are consistent with the idea that conditioned aversions to all exteroceptive stimuli are not equally well potentiated by taste.

Animals↗

PubMed1988

Salt preference in rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain).

Brattleboro rats are homozygous for diabetes insipidus (HO-DI), lacking the ability to synthesize vasopressin. Besides increasing water consumption, HO-DI rats may compensate for their excessive renal water loss by reducing their intake of and preference for substances that elevate plasma osmolarity. In two experiments we assessed this possibility. In Experiment 1, salt preference of HO-DI and control Long-Evans (LE) rats was measured by presenting the rats with two tubes: one filled with water and the other with NaCl. In the first part of the experiment, 18 NaCl concentrations were presented in increasing order (from 6 to 300 mM). In the second part, other groups of HO-DI and LE rats were presented with 6 concentrations of NaCl, ranging from 6 to 450 mM in either increasing or decreasing order of concentrations. In Experiment 2, preference for 6 concentrations of citric acid ranging from 0.1 to 6 mM was assessed. With NaCl concentrations greater than 100 mM, intake and preference declined rapidly for the HO-DI group but very gradually for the LE group. In contrast, the HO-DI rats preferred all citric acid solutions more than LE rats. The results suggest that HO-DI rats compensate for their inability to concentrate urine not only by increasing water consumption, but also by decreasing consumption of and preference for salty solutions.

Animals↗

PubMed1987

Conditioned taste aversion in vasopressin-deficient rats (Brattleboro strain).

Brattleboro rats are homozygous for diabetes insipidus (DI), lacking the ability to synthesize vasopressin. Previous studies reported learning deficits in DI rats on passive avoidance tasks using footshock. Other studies, however, could not replicate these results. In two experiments, we studied the learning of DI and control Long Evans (LE) rats in a different avoidance paradigm: conditioned taste aversion (CTA). In the first experiment a mild CTA to saccharin was established gradually using low levels of an illness-inducing agent (lithium chloride). In the second experiment a strong CTA was established in one acquisition trial and the extinction of the conditioned aversion was followed for 12 trials. The two experiments found no differences between the DI and LE rats in either the magnitude or the rate of acquisition and extinction of the CTA. These results suggest that vasopressin is not involved in the acquisition and retention of CTA, and support previous studies indicating that vasopressin may not be involved in avoidance learning.

Animals↗

PubMed1987

Role of temporal order and odor intensity in taste-potentiated odor aversions.

The role of the temporal order of odor and taste was studied in two experiments, and a third experiment studied the role of odor intensity in flavor-toxicosis conditioning with thirsty rats licking water spouts in a "wind tunnel." In all experiments, odors and tastes were presented for 2 min to rats, and 30 min later, a toxin (lithium chloride) was intubated. In Experiment 1, an odor was presented 90 s before, during, or 90 s after a taste to independent groups. Experiment 2 was a within-subjects partial replication of the first. Each rat was presented with one odor, then a taste, then a second odor with each stimulus separated by 45 s. The results of Experiments 1 and 2 indicated that (a) odor alone is not associated with illness under our conditions, (b) presenting an odor and a taste at the same time potentiates the odor component so that it is associated with illness, (c) 45-s and 90-s intervals between odor and taste eliminate potentiation, and (d) taste and odor interact asymetrically; that is, odor has little affect on the development of taste-illness associations. In Experiment 3, an odor and a taste were presented simultaneously, and odor intensity varied. As odor intensity increased, the strength of the taste-potentiated odor aversion increased, whereas the aversion to the taste remained constant. However, even at the highest intensity, odor presented in the absence of taste did not result in odor aversions.

Animals↗

PubMed1985

Effect of classical conditioning on an internal clock.

Six experiments with rats used a psychophysical choice procedure to study the internal clock used to discriminate duration. They investigated if the clock is sensitive to the signal value (associative strength) of a stimulus. The experiments involved two types of trials. On choice trials, a stimulus lasted a short (e.g., 3 s) or long (e.g., 12 s) duration; then the rats chose between two levers. The rewarded choice depended on the duration of the stimulus. On conditioning trials, the stimulus used on choice trials was presented, but it ended without food (extinction trials) or with food (pairing trials) regardless of what the rat did. The main stimulus minus accuracy with the long stimulus. Experiment 1 showed that extinction trials increased short bias relative to training without conditioning trials or to training with pairing trials. The rest of the experiments tested explanations of these results. The same results were found when extinction trials were the same duration as the short stimulus (Experiment 2), when extinction trials were a random duration (Experiment 5), and when the signal value of the conditioned stimulus was changed in another way (Experiment 6). The effect of conditioning trials was modality specific (Experiments 3 and 4). Of the explanations considered, the best one--the only one not contradicted at least once--is that changing the signal value of a stimulus changes how the clock times the stimulus. Reducing signal value reduces the measured duration.

Animals↗