Wesley C. Lynch

Opiate blockade inhibits saccharin intake and blocks normal preference acquisition.

Recent evidence indicates a close connection between oral sensory function and opioid effects on feeding. Not only is gustatory motivation influenced by opiate drugs but apparently gustatory stimuli can also activate central opiate receptor systems. In 3 experiments we studied the effect of opiate receptor blockade on drinking motivated by the sweet taste of saccharin. Experiment 1 established a dose-response function for inhibition of intake by naloxone (NAL) in short (60 min) 2-bottle tests. This experiment demonstrated the extreme sensitivity of nondeprived, nonstressed animals to NAL and estimated the MED50 at less than 0.1 mg/kg (SC), well below the threshold for effects due to illness or general motor disturbance. Experiment 2 further demonstrated that NALs effectiveness depends on saccharin concentration. In particular, the lowest NAL dose studied was effective near the threshold for saccharin preference but not at higher concentrations. These data suggest that endogenous opioid systems may be activated by taste stimuli in a graded fashion. Finally, experiment 3 showed that the typical acquisition of preference for a moderate saccharin concentration can be effectively blocked by daily pre-test NAL injection. Together these experiments further demonstrate the close functional relationship between opioid systems and gustatory sensory systems.

Naloxone suppresses intake of highly preferred saccharin solutions in food deprived and sated rats

In repeated tests naloxone (1 mg/kg, sc) suppressed intake of a narrow range of highly preferred saccharin concentrations (0.1 and 1.0%) in nondeprived male rats but a wider range of concentrations (.001-1.0%) following 10 hr. food deprivation. In sated rats a low dose of morphine (0.1 mg/kg, sc) had no effect on intake of low concentrations of saccharin but significantly facilitated intake of the highest (10%) and least preferred concentration. These data support the hypothesis that endogenous opioids can modulate the affective quality of gustatory stimuli.

Does binge eating play a role in the self-regulation of moods?

Self-reported emotional experiences and eating behaviors were studied in college students in an attempt to determine what types of emotional experiences precede and follow binge eating and how specific types of compensatory behaviors modify these experiences. First-year male and female students (N=390) were surveyed for depression, anxiety, health status, life satisfaction, and eating attitudes (EAT-26). Those reporting recurrent binge eating episodes were asked to describe their emotional feelings before and after bingeing and before and after compensatory activities. EAT-26 scores corresponding to scores previously reported for eating disordered patients were found in 9.7% of students. Binge eating was nearly twice as frequent among females (16.4%) as males (8.6%) Among females, positive relationships were found between specific EAT-26 factors scores and both anxiety and depression scores. The emotional antecedents and consequences of binge eating and of compensatory activities were compared in three sub-groups of individuals who reported recurrent bingeing with loss of self-control during binges. The three sub-groups consisted of individuals who reported, 1) bingeing without engaging in compensatory activities, 2) bingeing and compensating by means other than vomiting (fasting, exercising, or use of laxatives or diuretics), and 3) bingeing and compensating by vomiting. Regardless of the type of activity, those individuals who engaged in compensatory activities reported greater negative affect preceding binge episodes than those who did not compensate. In addition, contrary to expectations, negative affect did not decrease, but instead increased significantly, following binge episodes and decreased immediately before and after compensatory activities.

Unilateral Nostril Breathing Influences Lateralized Cognitive Performance

Relative nostril efficiency (nasal cycle) is related to hemispheric EEG differences and performance on cognitive tasks. We investigated how unilateral forced nostril breathing influences spatial and verbal performance. Right-handed males and females performed both tasks under either left-nostril, right-nostril, or free-breathing conditions. Unilateral breathing affects performance differently in males and females. It influences male performance ipsilaterally on both tasks: Their spatial performance is better during right-nostril breathing, and their verbal performance is better during left-nostril breathing. Unilateral breathing influences female performance contralaterally, but only on the spatial task: Their spatial performance is better during left-nostril breathing. These differences within and between sexes may exist because unilateral nostril breathing differentially activates the two hemispheres and thereby facilitates performance, or because attempts of the brain to control the nasal cycle unilaterally interfere with performance.

Effects of neuropeptide Y on ingestion of flavored solutions in nondeprived rats

Recent evidence suggests that in addition to altering energy balance, neuropeptide Y (NPY) may stimulate ingestive behavior by modifying the orosensory quality of ingested substances. The present experiments investigated the effect of intracerebroventricular administration of NPY (5 micrograms/5 microliters) on ingestion of various flavored solutions in nondeprived rats. Experiment 1 examined the effects of NPY on ingestion of a range of concentrations of saline, sucrose, and saccharin solutions in single-bottle tests. Results indicated that NPY stimulates ingestion of both sucrose and saccharin solutions that are normally palatable. In Experiment 2, palatable sucrose solutions flavored with either orange or black cherry Kool-Aid for separate training groups were selectively associated with NPY injection during single-bottle training sessions. Subsequent two-bottle preference tests showed a significant shift in preference toward the flavor paired with NPY during training. The results of these experiments extend previous findings by showing that NPY can stimulate ingestion of sweet solutions regardless of caloric value and may potentiate sweet taste preference via an associative mechanism.

Heterogeneous distribution and upregulation of μ, δ and κ opioid receptors in the amygdala

Abstract Levels of μ, δ and κ opioid receptors in 4 subnuclei of the rat amygdala were determined by quantitative autoradiography following chronic treatment with naloxone or saline. A different distribution of each receptor subtype was observed, with μ binding greatest in the lateral nucleus (La), δ greatest in the basolateral (B1), and κ greatest in the medial (Me). Levels of all 3 receptors were very low in the central nucleus. Receptor upregulation following chronic naloxone treatment was also anatomically heterogeneous. Increases in μ receptors were statistically significant in the Me, Bl and La, while increases in δ and κ receptors were significant only in the Bl.

Neuropeptide Y attenuates satiety: evidence from a detailed analysis of patterns ingestion

Centrally injected neuropeptide Y (NPY) is a potent stimulant of ingestive behavior capable of augmenting both food and fluid intake in fully satiated animals. To gain further insight into NPYs mechanism of action, we recorded patterns of licking behavior in rats drinking sweetened condensed milk solutions immediately after lateral ventricular injection of NPY (10 micrograms) or vehicle. In a separate study, we examined licking patterns after 23 h food deprivation (FD) that produced approximately the same total intake as NPY. Consistent with previous reports, we found NPY stimulated intake by increasing total ingestion time and total volume consumed during a 1-h test. Although NPY increased the number of bouts of licking and shortened pauses between bouts, it also decreased mean bout size, bout duration and within-bout lick rate (local rate). It had no significant effect on start latency or lick efficiency (licks/ml). Further analyses revealed that NPY attenuated satiety (reduced slope of lick-rate functions with session time) but had no significant effect on the beginning lick rate, a measure related to orosensory excitation. In contrast to NPY, FD increased both the beginning lick rate and individual bout size without changing either the mean number of bouts or the pause between bouts. In general, NPY stimulated an intermittent pattern of licking and delayed satiation whereas FD increased the initial rate of licking and the size of individual bouts without changing the basic licking pattern. The increase in initial lick rate suggests that FD, unlike NPY, enhances orosensory stimulation. These data compliment previous results showing that NPY increases the motivation to eat.(ABSTRACT TRUNCATED AT 250 WORDS)

Body dissatisfaction mediates the association between body mass index and risky weight control behaviors among White and Native American adolescent girls

The developmental path leading to eating disorders among adolescent girls often proceeds from increasing body size, to increasing body dissatisfaction, to increasing eating disorder (ED) risk. To determine whether body dissatisfaction (BD) mediates the association between body size and risky weight control behaviors, we examined data from White (n=709) and Native American (n=253) girls, who differ substantially in terms of average body mass and reported weight control behaviors. Measures of BD included weight, shape, and appearance concerns. Measures of ED risk included dieting, exercising to control weight, binge eating, and vomiting. Results showed body dissatisfaction was a highly significant mediator of the relationship between body mass index (BMI) and ED risk for both ethnic groups; although, BD did not mediate the association between BMI and binge eating for either group. BD is apparently an important mediator of the association between body size and some, but not all, risky weight control behaviors.

Opioid effects on intake of sweet solutions depend both on prior drug experience and on prior ingestive experience.

Two experiments investigated the effect of opioids on ingestion of sweet solutions in non-deprived rats. Experiment 1 replicated previous work from our laboratory showing virtually complete inhibition of sucrose and saccharin intake during 10 days of daily naloxone treatment. During recovery, prior naloxone experience significantly stimulated sucrose intake but had no effect on saccharin intake. In the absence of naloxone treatment, ingestive experience alone reduced naloxones typical intake-suppressant effect. These findings suggest that drug experience and ingestive experience may interact to determine the intake-suppressant effect of naloxone. Experiment 2 examined the effects of opioid agonists on sucrose ingestion during 10 days of initial drug treatment and 5 days of recovery. A low dose of the kappa agonist U-50,488H significantly stimulated sucrose ingestion during the drug treatment period and this effect persisted for several days after treatment ended. Initial (non-significant) intake suppressant effects of the mu agonist morphine or a high dose of U-50,488H tended to decrease with repeated testing and did not reappear during recovery. These data suggest that in addition to immediate, direct effects on motivation, opioids may affect long-term changes in responsiveness to sweet tastes.

Neurotensin-induced hypothermia prevents hippocampal neuronal damage and increased locomotor activity in ischemic gerbils

Hypothermia induced by surface cooling has shown to protect vulnerable regions of the brain during an ischemic insult. This study evaluated the neuroprotective efficacy of neurotensin, a potent hypothermic agent, using a 5-min carotid occlusion procedure in the gerbil. In Experiment 1, the dose-response and time course of neurotensin-induced hypothermia were evaluated (n = 5/dose). Central infusion of 10, 20, and 30 micrograms neurotensin were found to significantly decrease core body temperature of conscious gerbils within 30 min of administration. In Experiment 2, gerbils pretreated with 30 micrograms neurotensin were permitted to become hypothermic or were maintained at 37 degrees-38 degrees C (rectal) during ischemic insult. Other gerbils were pretreated with peptide vehicle prior to ischemic insult (at 37 degrees -38 degrees C) or underwent a sham procedure (n = 6/condition). At 24 h after surgery, gerbils were tested for increased locomotor activity in an open-field apparatus. Gerbils pretreated with peptide vehicle or neurotensin and maintained at 37 degrees-38 degrees C during ischemia had significantly higher activity levels compared to the other treated groups. In contrast, gerbils made hypothermic with neurotensin exhibited activity levels similar to sham gerbils. Histological assessment revealed that neurotensin-induced hypothermia protected the CA1 region from ischemic damage.