The association between obstructive sleep apnea and dietary choices among obese individuals during middle to late childhood

Objective

Determine whether obstructive sleep apnea (OSA) is associated with the dietary choices of obese individuals during middle- to late-childhood. It was hypothesized that OSA would be associated with increased caloric content of a dinner order, particularly with high carbohydrate food choices. Secondarily, we examined the relationships between sleep duration and dietary choices.

Methods

42 obese subjects aged 10–16.9 years participated in a cross-sectional study that involved systematic collection of sleep duration (based on actigraphy), presence and severity of obstructive sleep apnea (obstructive apnea + hypopnea index [AHI] from inpatient polysomnography) and the macronutrient content of dinners ordered from a standardized hospital menu the evening before the polysomnogram.

Results

Primary analyses using Spearman rank-order correlations found that AHI was significantly associated with total calories, as well as grams of fat and carbohydrate, but not protein. These macronutrient variables did not correlate with sleep duration across a week, nor the night before the meal. Findings were unchanged after correcting for age- and sex-adjusted BMI.

Conclusions

More severe OSA appears to be associated with an increased preference for calorie-dense foods that are high in fat and carbohydrates in a manner that is independent of degree of obesity. Although this novel finding awaits replication, it has potential implications for the clinical care of obese youth and individuals with OSA, adds to the limited data that relate sleep to dietary choices and may have implications for OSA-related morbidity.     

Genetics in the analysis of behaviour

Behaviour genetics has developed rapidly in the last two decades and has now gone far beyond the stage of merely measuring the extent to which individual differences on a particular behaviour can be attributed to genetic factors. This paper discusses the uses to which genetics can be put in efficient experimental design, in determining the generality of results and, most importantly, in the simultaneous analysis of several behaviours and their relationship to each other and to physical and biochemical parameters. Because the principles of genetics apply to all organisms, the first animal discussed is Drosophila, the vinegar fly, which is a vital tool in genetics but which has met with scant attention among psychologists. Drosophila has some unique advantages such as the sex mosaic technique for studying sexual behaviour, but most of the discussion concerns learning and the extent to which parallels can be found between Drosophila and the vertebrates, both in terms of process and of genetic control. It is demonstrated how strain differences and the response to artificial selection can distinguish between learning and other components of behaviour. Drosophila are also used to explain how the type of genetic control can suggest the way in which natural selection acts upon the particular behaviour and further examples from rodents are discussed to show that this is a general result across species. There are many inbred strains and selection lines of mice and rats and examples from a wide range of behaviours illustrate the advantages of using such stocks. The concept of the ‘behavioural phenotype’ is explained, where genetic differences on a wide range of behaviours are considered, rather than just focusing on one behaviour or one response to a particular drug or environmental treatment. Many different aspects of open-field behaviour, learning and mother-infant interaction are used as examples of this concept. The extent of genotype-environmental interaction is considered, since the possibility that each genotype will have a unique response to a particular treatment has considerable implications for the generality and replicability of results. The paper concludes with a brief discussion of human behaviour genetics, since here again the concern is not just with the trivial question of measuring ‘heritability’, but rather with how such information can be used to understand behaviour. The final suggestion is that psychology may gain by having more contact not only with geneticists, but also with the ecologists concerned with the significance of behavioural differences in the wild.     

Genetics in the analysis of behaviour

Behaviour genetics has developed rapidly in the last two decades and has now gone far beyond the stage of merely measuring the extent to which individual differences on a particular behaviour can be attributed to genetic factors. This paper discusses the uses to which genetics can be put in efficient experimental design, in determining the generality of results and, most importantly, in the simultaneous analysis of several behaviours and their relationship to each other and to physical and biochemical parameters. Because the principles of genetics apply to all organisms, the first animal discussed is Drosophila, the vinegar fly, which is a vital tool in genetics but which has met with scant attention among psychologists. Drosophila has some unique advantages such as the sex mosaic technique for studying sexual behaviour, but most of the discussion concerns learning and the extent to which parallels can be found between Drosophila and the vertebrates, both in terms of process and of genetic control. It is demonstrated how strain differences and the response to artificial selection can distinguish between learning and other components of behaviour. Drosophila are also used to explain how the type of genetic control can suggest the way in which natural selection acts upon the particular behaviour and further examples from rodents are discussed to show that this is a general result across species. There are many inbred strains and selection lines of mice and rats and examples from a wide range of behaviours illustrate the advantages of using such stocks. The concept of the ‘behavioural phenotype’ is explained, where genetic differences on a wide range of behaviours are considered, rather than just focusing on one behaviour or one response to a particular drug or environmental treatment. Many different aspects of open-field behaviour, learning and mother-infant interaction are used as examples of this concept. The extent of genotype-environmental interaction is considered, since the possibility that each genotype will have a unique response to a particular treatment has considerable implications for the generality and replicability of results. The paper concludes with a brief discussion of human behaviour genetics, since here again the concern is not just with the trivial question of measuring ‘heritability’, but rather with how such information can be used to understand behaviour. The final suggestion is that psychology may gain by having more contact not only with geneticists, but also with the ecologists concerned with the significance of behavioural differences in the wild.     

Buspirone-induced carbohydrate feeding is not influenced by route of administration and nutritional status

Rats were habituated to ad lib food intake from two isoenergetic diets that differed in carbohydrate and protein content. To examine the route of administration effect, buspirone (0.6, 1.0, and 1.4 mg/kg) was injected into satiated rats either subcutaneously or intraperitoneally. Overall, no route of administration effect was observed; however, when results of the lowest dose were analyzed separately, the subcutaneous route was more effective than the intraperitoneal route. Regardless of route of administration, buspirone increased food intake over the first 2 h of food presentation in a dosedependent manner. Moreover, the increase was entirely attributed to increases in intake from the high carbohydrate diet. In the subsequent experiment, the effect of buspirone (0.6 mg/kg) was examined in both satiated (early light period) and nonsatiated rats (early dark period). Both groups responded to buspirone with an increase in carbohydrate intake. Despite differences in baseline intake, the absolute increase was similar between satiated and nonsatiated rats. These data suggest that both sensitivity and selectivity of buspirone-induced feeding are neither influenced by route of administration nor nutritional status of rats.     

Brain mechanisms and the quantitative and qualitative aspects of food intake

The brain receives a large number of signals from the ingestion of food. They provide the brain with information on both the adequacy of energy ingested and the macronutrient composition of the food. From this information brain feeding control systems are able to respond and direct the animal to make appropriate food choices so that both the quantitative (energy) needs as well as the qualitative (nutrient) needs are met. An understanding of brain mechanisms regulating feeding will only emerge if their dual purposes are recognized.     

Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats

The acute effects of the party drug 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) in humans include feelings of love, closeness towards other people and an increased acceptance of others views and feelings. Some evidence suggests that regular MDMA users develop a subsensitivity to the positive effects of the drug and escalate their intake of the drug over time as a result. The current study investigated whether brief exposure to relatively high doses of MDMA in rats produces a subsequent attenuation in the ability of MDMA to enhance social interaction. Male Wistar rats were exposed to either MDMA (4 × 5 mg/kg over 4 h) or vehicle on two consecutive days. Twelve weeks later, MDMA pre-exposed rats displayed a significantly shorter period of time spent in social interaction than controls when tested in the drug-free state. MDMA pre-exposed rats also showed a blunted prosocial response to MDMA (2.5 mg/kg) relative to controls. This difference was overcome by increasing the MDMA dose to 5 mg/kg. The 5-HT_1A agonist 8-OH-DPAT (250 µg/kg but not 125 µg/kg) increased social interaction and this effect did not differ in MDMA and vehicle pre-exposed rats. HPLC analysis showed a small but significant depletion of prefrontal 5-HT and 5-HIAA in MDMA pre-exposed rats. Prefrontal 5-HIAA concentrations were also reduced in the subset of vehicle and MDMA pre-exposed rats that received additional testing with MDMA. These results indicate that treatment with MDMA not only causes lasting reductions in social interaction in rats but causes an attenuation of the prosocial effects of subsequent MDMA administration. The lack of a differential response to 8-OH-DPAT agrees with other findings that the 5-HT_1A receptor system remains functionally intact following MDMA pre-exposure and suggests that other neuroadaptations may underlie the lasting social deficits caused by MDMA.     

A comparison of the effects of the 5-HT1 agonists TFMPP and RU 24969 on feeding following peripheral or medial hypothalamic injection.

Experiments were conducted to compare the food intake suppressant effects of the 5-hydroxytryptamine (5-HT)₁ agonists 1-3-trifluoro-methylphenylpiperazine hydrochloride (TFMPP) and 5-methoxy-3-(1,2,3,6-tetrahydropyridinyl)1H indole (RU 24969) following either peripheral or medial hypothalamic injections. The effects of these manipulations were examined in 3 different paradigms involving the stimulation of feeding by: (1) infusion of 25 nmol noradrenaline (NA) into the medial hypothalamus, (2) adaptation to a 20 h food deprivation schedule, and (3) the presentation of a palatable wet mash diet for 1 h each day to ad libitum-fed rats. In all 3 paradigms TFMPP and RU 24969 (0.31–5 mg/kg, i.p.) induced dose-dependent reductions of food intake. Both drugs were somewhat less potent at inhibiting feeding that resulted from food deprivation. In contrast to these results medial hypothalamic infusion of TFMPP or RU 24969 (12.5–50 nmol) failed to affect food intake in any of the 3 tests. This occured in spite of the fact that both 5-HT (12.5–50 nmol) and fluoxetine (12.5–50 nmol) mildly attenuated the feeding that resulted from NA infusion into the same site. The results provide clear evidence that the food intake suppressant effects of peripherally injected TFMPP and RU 24969 are not mediated in the medial hypothalamus. They also suggest that even though manipulations of serotonergic function within the medial hypothalamus can alter food intake, this probably does not involve selective activation of 5-HT_1C and/or 5-HT_1B receptors.     

Nutritional influences on dietary selection patterns of obese and lean Zucker rats

Little is known about the behavioral, nutritional, and metabolic events that control dietary intake quality. Two experiments are described that manipulate nutritional conditions that have been hypothesized to affect dietary item choice so as to assess what effect, if any, the added factor of genetic obesity has in modifying the response to these manipulations. In the first experiment, 5 week old male obese and lean Zucker rats were fed a diet that varied in protein content (10%, 20%, or 60% casein by weight) for ten weeks. They were then allowed to select a diet from three separate macronutrient sources (casein, starch, or corn oil). Although body weights at the end of the 10 week maintenance period were markedly different, selection patterns were not influenced by pre-feeding different levels of protein. Obese rats selected a diet that was higher in fat and lower in protein than the diets composed by lean rats. In the second experiment, four groups of 7 month old obese and lean Zucker rats were given access to one of four diets that varied in protein content (5%, 10%, 15%, or 20% casein by weight). In addition, each rat was periodically given access to a 32% sucrose solution. Access to sucrose promoted increases in total caloric intake, independent of the protein content of the diet. Obese rats typically ate more calories per day than did their lean littermates. Results from these experiments suggest that food item selection is determined more by factors associated with obesity than by factors associated with dietary history.     

A comparison of the effects of the 5-HT1 agonists TFMPP and RU 24969 on feeding following peripheral or medial hypothalamic injection

Experiments were conducted to compare the food intake suppressant effects of the 5-hydroxytryptamine (5-HT)₁ agonists 1-3-trifluoro-methylphenylpiperazine hydrochloride (TFMPP) and 5-methoxy-3-(1,2,3,6-tetrahydropyridinyl)1H indole (RU 24969) following either peripheral or medial hypothalamic injections. The effects of these manipulations were examined in 3 different paradigms involving the stimulation of feeding by: (1) infusion of 25 nmol noradrenaline (NA) into the medial hypothalamus, (2) adaptation to a 20 h food deprivation schedule, and (3) the presentation of a palatable wet mash diet for 1 h each day to ad libitum-fed rats. In all 3 paradigms TFMPP and RU 24969 (0.31–5 mg/kg, i.p.) induced dose-dependent reductions of food intake. Both drugs were somewhat less potent at inhibiting feeding that resulted from food deprivation. In contrast to these results medial hypothalamic infusion of TFMPP or RU 24969 (12.5–50 nmol) failed to affect food intake in any of the 3 tests. This occured in spite of the fact that both 5-HT (12.5–50 nmol) and fluoxetine (12.5–50 nmol) mildly attenuated the feeding that resulted from NA infusion into the same site. The results provide clear evidence that the food intake suppressant effects of peripherally injected TFMPP and RU 24969 are not mediated in the medial hypothalamus. They also suggest that even though manipulations of serotonergic function within the medial hypothalamus can alter food intake, this probably does not involve selective activation of 5-HT_1C and/or 5-HT_1B receptors.     

Exposure to maternal consumption of cafeteria diet during the lactation period programmes feeding behaviour in the rat

Lactational overfeeding programmes obesity in the adult rat, and also impacts on adult emotional behaviour. The present study investigated the impact of exposing the lactating female to a hypercaloric diet on structural aspects of feeding behaviour in the adult offspring as measured by the behavioural satiety sequence (BSS). Lactating Wistar rats were fed a hypercaloric cafeteria diet (CD) in addition to chow. Controls were fed on chow only. All offspring were chow fed after weaning. BSS was tested in 12-15 week old offspring. At 20 weeks of age, monoamine neurotransmitter levels were measured in selected brain regions. When exposed to a palatable 1-h test meal, offspring responded with the same latency to feed, regardless of lactational diet. Total food intake during the test was unaffected by lactational diet. Control offspring showed a normal BSS pattern. Male CD offspring displayed shorter feeding bouts (P < 0.05) with an overall higher bout frequency (P < 0.001) and their latency to rest was delayed (P < 0.001). Overall eating frequency (P < 0.05), but not duration was increased in male CD offspring. Although the transition from feeding to resting was not affected by lactational CD, CD males fed for longer at the beginning of the test meal and were more active towards the end. CD females displayed an increased number of feeding bouts (P < 0.05) and they spent more time eating (P < 0.05). Resting latency was delayed (P < 0.05) and overall time spent resting was shortened (P < 0.01). Frequency of eating was increased in the middle of the test meal. The onset of satiety as indicated by the transition point between eating and resting was delayed in CD females (P < 0.001). In both sexes, hypothalamic 5-hydroxytryptamine (5-HT) was increased (P < 0.05 in females, P < 0.01 in males) and 5-HT turnover was reduced by lactational CD (P < 0.001 in females, P < 0.01 in males). Lactational CD led also to an increase in dopamine (DA) (P < 0.01). Hypothalamic DA metabolism (DOPAC + HVA/DA ratio) was overall lower in females than in males (P < 0.01). This study indicates a programming effect of lactational CD on feeding behaviour and brain monoaminergic neurons.     

5-Hydroxytryptamine stimulates stimulates corticosteroid-sensitive CRF release from cultured foetal hypothalamic cells. Role of protein kinases

5-Hydroxytryptamine (5-HT) has been shown to activate the hypothalamo-pituitary-adrenal axis, possibly by a direct action on hypothalamic CRF synthesis and release. In order to study the mechanisms involved in this effect, foetal hypothalamic cells were cultured and corticotropin-releasing factor-41 (CRF) release was measured by radioimmunoassay. 5-HT induced CRF release in a dose-dependent manner. Further studies were performed with a specific protein kinase C inhibitor, H-7 (1-(5-isoquinolinesulfonyl)-2-methyl-piperazine) and a specific cyclic adenosine monophosphate-dependent protein kinase inhibitor, IP-20. Basal release of CRF-41 from the cultured hypothalamic cells was unaffected by IP-20 and was only diminished at a high (50 microM) concentration of H-7. 5-HT stimulated-CRF release, however, was blocked by both H-7 and IP-20. Dexamethasone and aldosterone both caused a dose-dependent inhibition of 5-HT induced CRF release. These results demonstrate that CRF can be released from hypothalamic neurons in response to 5-HT through a protein kinase C and protein kinase A dependent mechanism and that 5-HT stimulated CRF release can be inhibited by dexamethasone and aldosterone.     

Neonatal monosodium glutamate alters circadian organization of feeding, food anticipatory activity and photic masking in the rat

In rodents, parenteral administration of monosodium glutamate (MSG) induces marked degeneration of the retina and arcuate nucleus (AN) and disrupts daily rhythms of food intake. We quantified the effects of neonatal MSG (2 mg/g SC, postnatal days 1, 3, 5, 7, 9) on the expression of feeding and activity rhythms in adult rats under schedules of light-dark (LD), constant dark (DD), restricted daily feeding and total food deprivation. AN lesions were confirmed by neuropeptide Y (NPY) immunocytochemistry and Nissl stain. Compared to age-matched control rats, the amplitude (quantified as LD ratios) of daily food intake and food-bin activity rhythms was significantly attenuated in MSG rats in LD 12:12 and on the first day of DD. Control rats, but not MSG rats, showed lower amplitude rhythms in DD compared to LD. The phase angle of feeding and activity rhythms did not differ between groups in either condition. In a short LD cycle (2:2), control rats, but not MSG rats, showed significant inhibition (masking) of activity during the 2 h light periods. When food access was restricted to a 4 h daily meal, MSG rats showed enhanced expression and persistence of food-entrained anticipatory activity rhythms by comparison with control rats. These results indicate that attenuation of daily feeding rhythms in MSG rats is due in part to loss of direct inhibitory effects of light on behavior, and that the AN likely modulates, but does not mediate entrainment of feeding-related rhythms to daily cycles of LD or food access.     

The action of(±)-MDMA on medial prefrontal cortical neurons is mediated through the serotonergic system

The mechanism of action of systemitically administered(±)-MDMA (3, 4-methylenedioxymethamphetamine) on spontaneously active neurons in the medial prefrontal cortex (mPFc) of chloral hydrate anesthetized rats was examined using standard single unit extracellular recording techniques. Intravenously administered MDMA dose-dependently decreased the firing rates of the majority of mPFc neurons in control rats. In contrast, in rats that were pretreated withp-chlorophenylalanine (PCPA), which depletes the brain serotonin (5-hydroxytryptamine, 5-HT) content by inhibiting tryptophan hydroxylase, the rate-limiting enzyme in the synthesis of 5-HT, MDMA was largely ineffective in inhibiting the firing of mPFc cells. In PCPA-treated animals, the administration of 5-hydroxytryptophan (5-HTP), which presumably restored the brain 5-HT content, but notl-DOPA, reinstated MDMA's inhibitory action in PCPA-treated rats. In rats that were pretreated withα-methyl-p-tyrosine (AMPT), which depletes the brain dopamine (DA) content by inhibiting tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of DA, MDMA inhibited the firing of all of the mPFc cells. MDMA's effect on mPFc neurons was reversed by 5-HT receptor antagonists such as granisetron and metergoline. These results strongly suggest that MDMA exerts its action on mPFc cells indirectly by releasing endogenous 5-HT.     

Neuropeptide Y mRNA and serotonin innervation in the arcuate nucleus of anorexia mutant mice

The anorexia (anx) mutation causes reduced food intake in preweanling mice, resulting in death from starvation within 3–4 weeks. In wild-type rodents, starvation induces increased neuropeptide Y (NPY) mRNA levels in the arcuate nucleus that promotes compensatory hyperphagia. Despite severely decreased body weight and food intake at 3-weeks age, anx/anx mice do not show elevated NPY mRNA levels in the hypothalamic arcuate nucleus compared to wild-type/heterozygous littermates. The NPY mRNA levels can be upregulated in normal mice at this chronological age, because 24-h food deprivation increased arcuate NPY mRNA in wild-type littermates. The unresponsiveness of NPY expression in the arcuate of anx/anx mice was paralleled by serotonergic hyperinnervation of the arcuate nucleus, comparable to the serotonergic hyperinnervation previously reported in the rest of the anx/anx brain. This result is consistent with the hypothesis that wasting disorders are accompanied by disregulation of NPY mRNA expression in the arcuate nucleus, and suggests that reduced food intake, the primary behavioral phenotype of the anx/anx mouse, may be the result of altered hypothalamic mechanisms that normally regulate feeding.     

Effect of drugs influencing 5-HT function on ethanol drinking and feeding behaviour in rats: Studies using a drinkometer system

In the present study, we have investigated how various 5-HT agonists (m-chlorophenylpiperazine (mCPP) (0.1-1 mg/kg), 8-hydroxy 2-(di-N-propylamino) tetralin (8-OH DPAT) (0.125-2 mg/kg) and 5-HT (0.5-2 mg/kg)), the 5-HT uptake blocker sertraline (1-10 mg/kg), and the 5-HT uptake blocker and releaser dexfenfluramine (0.5-2.5 mg/kg), affect ethanol intake in a continual access paradigm using Wistar rats. By means of a drinkometer system the effect of each drug on microdrinking parameters (e.g., drink latency, number, and duration of drinking bouts) was assessed. The effect of various 5-HT antagonists (metergoline, ritanserin, ondansetron, and xylamidine) against the dexfenfluramine-induced suppression was studied. Furthermore, threshold doses for the anorectic and the suppressant effects of mCPP, sertraline and dexfenfluramine on ethanol intake were identified. From these studies, it seemed that similar mechanisms may be responsible for the suppressant effects of the various 5-HT agonists studied (direct and indirect) on ethanol and food intake. The 5-HT3 receptor antagonist, ondansetron, also reduced ethanol (but not food) intake. However, the profile of this effect may suggest an alternative means by which 5-HT3 receptors regulate ethanol intake in the rat by comparison to the various 5-HT agonists studied.     

Adaptation of female rats to stress: shift to male pattern by inhibition of corticosterone synthesis

In a previous study, male rats showed behavioural deficits after a single restraint stress but not after 5 daily restraint periods (i.e. adaptation had developed): female rats although less affected by single restraint failed to adapt over the same time course. This sex difference was associated with the male but not the female rats showing enhanced behavioural responses to the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) after 5 restraint periods. In the present study, the role of the greater increases of plasma corticosterone in stressed females in these sex differences was studied. The corticosterone synthesis inhibitor metyrapone (75 mg/kg i.p.) was given to attenuate the rise of corticosterone to a level typical of stressed males. This resulted in the behavioural deficits of the female rats being shifted in the direction of the male pattern. Thus, their deficits in open field activity and food intake after single and repeated stresses were potentiated and opposed respectively. The latter effect was associated with increased responses to 5-MeODMT. Metyrapone alone was without significant effect. Brain regional 5-HT metabolism was unaffected. The results are consistent with corticosterone facilitating adaptation to single restraint but impairing adaptation to repeated restraint. As failure to adapt to repeated stress is an animal model of depression, results as a whole suggest that increased corticoid levels and decreased 5-HT functional activity may have a role in the development of the illness and its greater incidence in women.     

Relationship between uptake of norepinephrine by hypothalamic homogenates and the activity of brown adipose tissue

It has previously been established that norepinephrine (NE) in the central nervous system is involved in feeding and the development of obesity. The present experiments were carried out to investigate the relationship between the uptake of NE by a crude hypothalamic homogenate and NE-mediated sympathetic activity in interscapular brown adipose tissue (IBAT). Sympathetic nervous system activity was assessed by measuring the binding of the purine nucleotide guanosine-5′-diphosphate (GDP) to mitochondria isolated from IBAT. Four situations known to alter food intake and sympathetic activity, namely, corticotropin releasing factor infusion, adrenalectomy, fenfluramine treatment and obesity due to genetic transmission were studied. In each case, [³H]NE uptake by the hypothalamic preparation and GDP binding to IBAT mitochondria were measured. A highly significant negative correlation between the uptake of NE by hypothalamic homogenates and the binding of GDP to IBAT mitochondria was obtained in both lean and obese animals. These findings are discussed with regard to the regulation of food intake and sympathetic nervous system mediated thermogenesis.     

Determination of the source of 5-hydroxytryptaminergic neuronal projections to the neural and intermediate lobes of the rat pituitary gland through the use of electrical stimulation and lesioning experiments

5-Hydroxytryptamine (5-HT)-containing axons and terminals have been visualized in the neural and intermediate lobes of the rat pituitary gland, but the origin of these fibers remains in question. This study was designed to determine if 5-HT cell bodies in the brainstem or in the dorsomedial nucleus of the hypothalamus project to either of these pituitary lobes. Since lesions and electrical stimulation of 5-HT cell bodies decrease and increase, respectively, the rate of 5-HT synthesis in regions innervated by these cells, these techniques were employed. The in vivo rate of 5-HT synthesis was determined by quantifying the rate of accumulation of the 5-HT precursor, 5-hydroxytryptophan (5-HTP), in the neural and intermediate lobes of the pituitary gland 30 min after the administration of a decarboxylase inhibitor (NSD 1015, 100 mg/kg, i.p.). The application of 30 min of stimulating current (monophasic cathodal pulses of 1 ms duration and 0.3 mA current delivered at a frequency of 10 Hz) to electrodes implanted in the dorsal and median raphe nuclei increased the rate of 5-HT synthesis in both the neural and intermediate lobes of the pituitary gland. 5,7-Dihydroxytryptamine lesions of these nuclei altered neither 5-HTP accumulation nor 5-HT concentrations in the neural and intermediate lobes, but similar lesions of the nuclei raphe pontis and raphe magnus decreased both the concentration of 5-HT and the accumulation of 5-HTP in these pituitary regions.(ABSTRACT TRUNCATED AT 250 WORDS)