Decreased Fluid Intake Research Articles

Effects of Parenteral Hydration in Terminally Ill Cancer Patients: A Preliminary Study

Most patients with cancer develop decreased oral intake and dehydration before death. This study aimed to determine the effect of parenteral hydration on overall symptom control in terminally ill cancer patients with dehydration. Patients with clinical evidence of mild to moderate dehydration and a liquid oral intake less than 1,000 mL/day were randomly assigned to receive either parenteral hydration with 1,000 mL (treatment group) or placebo with 100 mL normal saline administered over 4 hours for 2 days. Patients were evaluated for target symptoms (hallucinations, myoclonus, fatigue, and sedation), global well-being, and overall benefit. Twenty-seven patients randomly assigned to the treatment group had improvement in 53 (73%) of their 73 target symptoms versus 33 (49%) of 67 target symptoms in the placebo group (n=22; P = .005). Fifteen (83%) of 18 and 15 (83%) of 18 patients had improved myoclonus and sedation after hydration versus eight (47%) of 17 and five (33%) of 15 patients after placebo (P = .035 and P = .005, respectively). There were no significant differences of improvement in hallucinations or fatigue between groups. When blinded to treatment, patients (17 [63%] of 77) and investigators (20 [74%] of 27) perceived hydration as effective compared with placebo in nine (41%) of 22 patients (P = .78) and 12 (54%) of 22 investigators (P = .15), respectively. The intensity of pain and swelling at the injection site were not significantly different between groups. Parenteral hydration decreased symptoms of dehydration in terminally ill cancer patients who had decreased fluid intake. Hydration was well tolerated, and a placebo effect was observed. Studies with larger samples and a longer follow-up period are justified.

A randomized, placebo-controlled trial of parenteral hydration in terminally ill cancer patients

8004 Background: Most cancer patients develop decreased oral intake and dehydration before death. Parenteral hydration is provided to almost no patients in hospices and almost all patients in acute care facilities. Methods: 51 Patients with clinical evidence of mild to moderate dehydration and oral intake of less than 1000 ml per day were randomized to receive parenteral hydration with 1000 ml normal saline (SC or IV) versus placebo (100 ml normal saline SC or IV) over 4 hours on days 1 and 2. Patients were evaluated for target symptoms (hallucinations, myoclonus, fatigue and sedation), and global well being at baseline and on day 2 of the study using 0 to 10 numerical scales. Overall benefit of the treatment was assessed by the patient and the investigator using 1 to 7 scales. Results: 49 patients were evaluable (96%): 27 patients randomized to parenteral hydration had improvement in 53/73 (73%) evaluable target symptoms versus 33/67 (49%) in 22 patients who received placebo (p=0.005). 15/18 (83%) and 15/18 (83%) patients had improved myoclonus and sedation after hydration versus 8/17 (47%) and 5/15 (33%) after placebo (p=0.03 and p=0.005, respectively). There were no significant differences of improvement in hallucinations and fatigue. Patients assessed hydration as effective in 17/27 (63%) cases and placebo effective in 9/22 (41%) cases (p=0.78). Investigators found hydration was effective in 20/27 (74%) cases and placebo in 12/22 (54%) cases (p=0.15). The mean of pain and swelling at the injection site in subcutaneous hydration (n=20) and subcutaneous placebo (n=17) were 2.1 (+/-2.95) versus 1.75 (+/-2.55) (p=0.1), and 0.82 (+/-1.13) versus 1.41 (=/-1.66) (p=0.64), respectively. Conclusions: Parenteral hydration improved symptoms in terminally ill cancer patients with decreased fluid intake. Hydration was well tolerated and placebo effect were observed. Studies with longer follow-up are required. No significant financial relationships to disclose.

Estrogen Depletion Differentially Affects Blood Pressure Depending on Age in Long–Evans Rats

Normotensive female rats exhibit age-related decreases in estrous cyclicity and increases in blood pressure. In spontaneously hypertensive rats, estrogens, including dietary phytoestrogens, prevent or attenuate the increased blood pressure associated with estrogen depletion. The present studies examine the effects of ovariectomy (OVX) at either 3 or 10 mo of age. Although blood pressure increases from 3 to 9 mo, OVX at 3 mo of age has no added effect--despite the fact that OVX (compared to ovary-intact) rats weighed significantly more. In contrast, aging from 10 to 16 mo is associated with a further increase in blood pressure, which is potentiated by estrogen depletion. Removal of dietary phytoestrogens exacerbated the hypertensive effects of OVX in these middle-aged rats. As in younger rats, estrogen depletion at 10 mo of age was associated with greater weight gain. Whereas estrogen depletion at 3 mo of age was without effect on fluid intake over the next 6 mo, OVX at 10 mo of age was associated with decreased fluid intake. In a final study, rats were OVX at 3 mo of age with estradiol (E2) treatment initiated at 10 mo of age. Long-term OVX ( >10 mo) was associated with increased blood pressure and mortality at 14-16 mo of age. Circulating levels of E2 were decreased by OVX. Plasma aldosterone was increased by OVX, an effect which was prevented by either E2 or phytoestrogens. Neither E2 nor aldosterone was affected by age. These data indicate that (a) the physiological effects of estrogen depletion vary with age; (b) phytoestrogens in the diet exert some protective effects; and (c) long-term OVX in the absence of hormone re-placement is associated with premature mortality. We suggest that chronic increases in aldosterone and sympathetic tone underlie the hypertensive effects of estrogen depletion.

Fluid intake and risk of bladder and other cancers.

There are appreciable differences in total fluid intake at the individual and population level, and substantial difficulties in obtaining valid measures of fluid intake. Epidemiological studies have examined the association between fluid intake and different types of cancer. For bladder cancer, fluid consumption has been associated with a moderate increase of risk in some studies, including a multicentric case-control study from the United States, based on about 3000 cases, with a decrease in others, including the Health Professional Follow-up study, or with no material association. The evidence, therefore, is far from consistent. Sources and components of fluids were also different across different types studies. From a biological point of view, a decreased fluid intake could result in a greater concentration of carcinogens in the urine or in a prolonged time of contact with the bladder mucosa because of less frequent micturition. Carcinogenic or anticarcinogenic components of various beverages excreted in the urine may also play a role in the process. It has been suggested that fluid consumption has a favorable effect on colorectal cancer risk. Fluid intake may reduce colon cancer risk by decreasing bowel transit time and reducing mucosal contact with carcinogens. Low fluid intake may also compromise cellular concentration, affect enzyme activity in metabolic regulation, and inhibit carcinogen removal. However, epidemiological data are inadequate for evaluation. Data are sparse and inconsistent for other neoplasms, including breast cancer. The fluid constituent of foods, confounding, interactions and possible influences of specific types of beverages should be investigated further. In conclusion therefore the association between total fluid intake and cancer risk remains still open to debate.

Fluid Intake and the Risk of Tumor Recurrence in Patients With Superficial Bladder Cancer

High fluid intake has been associated with a decreased risk of bladder cancer development in men. We evaluated whether higher fluid intake can impact tumor recurrence rates in patients with superficial bladder cancer. We conducted a prospective single institution analysis of fluid intake in 267 consecutive patients with superficial bladder cancer undergoing routine bladder cancer surveillance between January 1998 and December 2001. Fluid intake questionnaires, urine cytology and physical examination were routinely performed at each surveillance cystoscopy. Cytological and histological recurrences were recorded. All patients had a minimum followup of 2 years. No relationship between fluid intake and tumor recurrence was demonstrated. Average daily fluid intake was 2,654 ml daily, which was well within the highest protective level (more than 2,531 ml) previously reported. However, multivariate analysis failed to show a protective effect against recurrence at any level of fluid intake. Increasing age correlated with decreased fluid intake (Pearson's correlation coefficient -0.19, p = 0.0015), but did not increase the risk of recurrence (p = 0.59). Single fluid intake data correlated with the average of additional fluid intakes (median 5 per patient) in the same patient (Pearson's correlation coefficient, 0.45, p < 0.0001). Of the study population 123 patients (46%) experienced 1 or more tumor recurrences (range 0 to 11) within a median followup of 2.6 years. Our prospective study of fluid intake in patients with superficial bladder cancer at risk for recurrence did not find any association between daily fluid intake levels and tumor recurrence.

Maintaining oral hydration in older adults: A systematic review

Dehydration is the most common fluid and electrolyte imbalance in older adults. The objectives were to identify the factors that increase the risk of dehydration in older adults, how best to assess the risk and manage oral fluid intake. Data sources included Medline, CINAHL, Cochrane Library, Embase and Current Contents, which were searched until February 2002. Randomized controlled trials for management of adequate fluid intake were undertaken. Cohort and case control studies were used for the identification of risk factors for dehydration. Studies of assessment tools for the identification of dehydration were also considered. Results show that there is no clear determination of the risk factors for dehydration and decreased fluid intake. The recommended daily intake of fluids should be not less than 1600 mL/24 h in order to ensure adequate hydration. A fluid intake sheet and urine specific gravity might be the best methods of monitoring daily fluid intake. Regular presentation of fluids to bedridden older adults can maintain adequate hydration status. In conclusion, more research is required to determine the optimum method of maintaining adequate oral hydration in older adults.

Acute Kawasaki Disease in Association with Burn Injury

While the etiology of Kawasaki disease (KD) is unknown, a role for infectious agents, including common skin organisms, has been proposed. We report 2 cases of KD associated with burn injury. Case 1: A 2 year old boy was admitted with a first and second degree scald injury to more than 9% of his body. Initial leukocyte count (WBC) was elevated. He was discharged to home the next day, and on daily visits was noted to have decreased fluid intake with fever without an infectious source. A generalized macular rash developed and he was readmitted with persistent fever. He subsequently developed conjunctivitis, oral changes and unilateral cervical lymphadenopathy with erythema of his palms. He had elevated WBC, ESR and liver transaminases. Acute KD was diagnosed and he received a single dose of IVIG on day 8 of his illness, with good response. All culture results were negative. Initial and follow-up echocardiograms were normal. Case 2: A 2 year old boy was transferred to hospital with second degree scald injury to 20% of his body. Within 24 hours he developed fever and cough, which continued without an infectious source for the next 6 days. He developed conjunctivitis and oral changes, with normal WBC, elevated ESR and normal liver transaminases. A diagnosis of atypical KD was considered, and he subsequently developed a generalized rash and extremity changes. A single dose of IVIG was given on day 8 of his illness, with good response. Initial echocardiogram showed mild dilation of the left main coronary artery, which resolved by his 6 week assessment. All culture results were negative. We speculate that the association of KD with burn injury in these patients may relate to stress or injury-induced immunologic changes, skin or tissue antigen release, or weakened barrier for entry of skin and other organisms

Neonatal Care of the Infant of the Diabetic Mother

After completing this article, readers should be able to: 1. Describe the most significant factor influencing neonatal morbidity in the diabetic pregnancy. 2. Characterize the impact of maintaining as normal a metabolic state as possible on the potential for perinatal and neonatal complications. 3. Describe the optimal location and services for delivery of a diabetic parturient. 4. Characterize the evaluation of an infant of a diabetic mother who requires resuscitation after birth. 5. Delineate the factor that most increases the chance of successful management of an infant of a diabetic mother in a regular nursery setting. Although many infants of diabetic mothers (IDMs) have an uneventful perinatal course, there is still an increased risk of complications, even in the infant born to the woman who has gestational diabetes. This discussion highlights specific factors that are critical in the immediate care of the IDM in the delivery room, in the nursery, and after discharge from the hospital. The care of this neonate builds on the pathophysiologic concepts presented in “The Infant of the Diabetic Mother” also appearing in this issue and other recent reviews of the subject. (1)(2) The physician responsible for the care and delivery of the parturient must inform the neonatologist, pediatrician, or their designee responsible for the care of the neonate of the mother’s condition well in advance of delivery to ensure optimal care of the newborn. Among the specific factors that are of utmost importance are the type of diabetes and degree of maternal control, prior pregnancy history, and complications occurring during the pregnancy, including data about fetal monitoring for determination of fetal size and maturation. This information allows the physician caring for the neonate to anticipate many, if not most, of the potential fetal and neonatal complications and assist in determining if a neonatologist needs to be present …

Maintaining Oral Hydration in Older People; A Systematic Review

Objectives The objective of this review is to present the best available evidence related to: • the factors that increase the risk of poor hydration in older people, • how best to assess older people for risk of inadequate fluid intake, presence and/or risk of dehydration, and • how best to maintain adequate oral fluid intake or hydration, or reverse dehydration, in older people. Criteria for Considering Studies for this Review Types of Participants This review considered all studies that included adults aged over 60 years in an acute care, residential care or community setting. Types of Intervention Interventions of interest were those related to the maintenance of oral hydration in older people, including interventions that ensured optimal fluid intake in older people. This review focussed on oral fluid replacement interventions only. Only oral rehydration management protocols were considered because techniques such as subcutaneous, intravenous and feeding tube fluid replacement are less common in community or nursing home settings. In addition to the management of older adults with inadequate fluid intake, this review also included studies that: 1) identified risk factors for poor fluid intake and dehydration, and 2) evaluated assessment tools to assist in determining fluid intake and fluid status in older people. Studies addressing the ethics of hydration in the terminally ill were excluded as beyond the scope of the review. Types of Outcome Measures The primary outcomes of interest were the measurement of oral fluid intake and those related to the identification of dehydration, the maintenance of oral hydration or the reversal of dehydration. Types of Studies This review considered any randomised control trial that evaluated management strategies to ensure adequate oral fluid intake and maintenance of hydration, or reversal of dehydration, in older people. For the identification of risk factors for dehydration in older people, cohort and case control studies were also included. Studies that evaluated assessment tools for the identification of dehydration in older adults were also considered for inclusion in this review. Results This review has been separated into three categories: risk factors, assessment, and management of dehydration/reduced fluid intake. Risk Factors Few studies have been performed to determine the risk factors for dehydration and/or reduced fluid intake. Age was determined to be a risk factor for dehydration in nursing home residents, but not in older adult emergency admissions. Age as a risk factor for reduced fluid intake yielded contradictory results. Bedridden patients were found to be at higher risk of dehydration, however semi-dependent older adults were found to be at most risk of reduced fluid intake in one study with no correlation in another. It was unclear from present studies if gender was a risk factor for either dehydration or reduced fluid intake. Incontinence was not found to be a risk factor for dehydration in one study but was for decreased fluid intake in another. Mental status was inversely correlated to risk of dehydration but contradictory results were obtained for reduced fluid intake. Reduced speaking ability and evidence of drooling identified patients as being more dependent however this reduced their risk of decreased fluid intake. A single study identified the presence of multiple diseases/medications as risk factors for dehydration. The number of ingestion sessions provided to nursing home residents was also positively correlated with fluid intake. Finally, one study concluded that being an institutionalised older adult led to an increased risk of a significantly lower fluid intake compared to older adults in the community. TRUNCATED AT 600 WORDS

Development of constipation in nursing home residents.

Constipation is a common complaint among geriatric patients and may result in significant morbidity, especially among nursing home residents. The prevalence of constipation increases with advancing age and may be a result of the aging process, but the exact cause is unknown. The aim of this study was to describe the prevalence of constipation and to determine risk factors for the development of constipation in a large population of nursing home residents. The Minimum Data Set is an assessment instrument used in nearly all Medicare-certified and Medicaid-certified nursing facilities. Nursing home residents who were at least 65 years of age and who had assessments at baseline and at three months were included in the study (N = 21,012). Baseline risk factors were included in a multivariate logistic regression to determine their association with the development of constipation. To allow causal implications, nursing home residents with constipation at baseline were excluded. The variables examined included medications, mobility, comorbid illness, and nutrition. The mean age (+/- standard deviation) of nursing home residents was 83 +/- 8 years, and the population was 70 percent female and 83 percent white. At baseline, the prevalence of constipation was 12.5 percent (N = 2,627). By the three-month assessment, 7 percent (N = 1,291) of nursing home residents had developed constipation. The factors associated independently with the development of constipation were, in order of magnitude, race, decreased fluid intake, pneumonia, Parkinson's disease, and the presence of allergies. Congestive heart failure and the use of a feeding tube were two factors identified as having a protective effect. The variables associated with the development of constipation may be used to identify geriatric nursing home residents at risk and to prevent constipation and its potential complications. Further study is needed to demonstrate a causal relationship between the risk factors and the development of constipation.

Index of Suspicion

1. Harminder S. Dhaliwal, MD 1. Columbia Medical Center, Lewisville, TX This section of Pediatrics in Review reminds clinicians of those conditions that can present in a misleading fashion and require suspicion for early diagnosis. Emphasis has been placed on conditions in which early diagnosis is important and that the general pediatrician might be expected to encounter, at least once in a while. The reader is encouraged to write possible diagnoses for each case before turning to the discussion, which is on the following page. We invite readers to contribute case presentations and discussions. A 5-year-old girl is seen because of 5 days of fever and worsening cough accompanied by nausea, poor appetite, and decreased fluid intake. She complains of right-sided back and shoulder pain and has difficulty walking. She has had no contact with ill persons. On physical examination, her rectal temperature is 38.9°C (102°F), pulse is 151 beats/min, respirations are 52 breaths/min, and oxygen saturation by pulse oximetry is 95% on room air. Her respirations are labored, rapid, and shallow, with nasal flaring, retractions, and occasional grunting. Inspiratory crackles are heard over the right lung base. Scattered palatal petechiae are present. Her abdomen is diffusely tender, without guarding or rebound tenderness. Her leukocyte count is 7,900/mm3, with 76% band forms, 5% metamyelocytes, and 2% myelocytes. Chest radiographs demonstrate complete opacification of the right middle lobe with a small right pleural effusion. The child is admitted for intravenous rehydration and broad-spectrum antibiotic therapy. Despite therapy, she develops moderate respiratory distress, vomiting, and oliguria. Computed tomography of the chest demonstrates a large right pleural effusion with early left mediastinal shift. A right thoracostomy tube is placed and 400 mL of fluid is evacuated. Despite these measures, the child’s condition continues to deteriorate. Her platelet count is 18,000/mm3; hematocrit, 15%; direct bilirubin level, 22 mg/dL; aspartate aminotransferase level, …

Index of Suspicion

Index of Suspicion

Cultural Perceptions of Diarrhea and Illness Management Choices among Yoruba Mothers in Oyo State, Nigeria

Home management of childhood illness is a norm throughout most of the world. Decisions about treatment are influenced by cultural perceptions of the illness, and diarrheal illnesses are no exception. A group of 473 mothers and their pre-school age children in rural communities outside Ibadan metropolis in Nigeria were followed over a two-month period. Data were collected on actual diarrhea illness episodes: mothers' names for these illnesses were recorded, and reported treatment actions were noted. Six major ethno-medical diarrheal illnesses were identified and were grouped broadly into watery diarrheas and dysentery-like diarrheas. Although few (40%) women used home-made sugar-salt solution (SSS) in case management, those who labeled their child's illness as a watery diarrhea were more likely to use SSS. Modern and herbal medicines were commonly and equally applied to both groups of diarrheal illnesses. While very few mothers reported decreased fluid intake by their children, many said the child had reduced appetite, especially if the child had a watery diarrhea. The findings indicate that twelve years after the national Oral Rehydration Therapy (ORT) Program was launched, few mothers practice the recommended actions of giving SSS, increasing food intake and avoiding drugs. Lack of attention to studies that describe the cultural basis for mothers' decisions could be part of the reason why the ORT has not been more successful.

Dehydration, Delirium, and Disability in Elderly Patients

To the Editor. —The article by Dr Ferrucci and colleagues ' on catastrophic and progressive disability helps physicians to understand the disability process in older persons. However, dehydration and cognitive impairment need more emphasis. First, Ferrucci et al found that dehydration was an important diagnosis in the disability subsets. Dehydration was 1 of the 6 most frequent discharge diagnoses among both men and women who developed progressive disability, and its cumulative percentage was similar to that of pneumonia and diabetes. 1 In fact, approximately 1.5% of community-dwelling elderly will be hospitalized with dehydration annually. 2 Drugs, diseases, and psychosocial factors that cause decreased fluid intake or increased fluid loss in older patients can predispose them to dehydration. 3 Consequently, dehydration is both effect and cause with respect to disability. For instance, dehydration may contribute to disability by weakness due to electrolyte imbalance. In 1991, Medicare beneficiaries hospitalized with dehydration were identified

Fluid intake and behavioral changes in rats associated with the distension of the small and large intestine.

Effects of volumetric distension of the small and the large intestine on rats' behavior were compared. Rats were stimulated by a rubber balloon inserted into chronic isolated intestinal loops prepared from the lower duodenum-upper jejunum and from the upper colon in the same animal. Thresholds of 3 reaction classes (weak, strong, and painful) were not different from each other in the 2 loops. Distension decreased fluid intake in an intensity-dependent way, with weak and painful stimuli being less effective in the large intestine and strong stimuli less effective in the small bowel. Behavioral indexes supported intake data, satiety indexes were similar to each other and changed in time, whereas aversivity indexes differed in the 2 loops and as a function of intensity but not time. The author suggests that mild discomfort is a physiological satiety factor whereas strong and painful stimuli signal danger and induce aversivity.

Susceptibility to high-altitude pulmonary edema in Madison and Hilltop rats. I. Ventilation and fluid balance

The pathogenesis of high-altitude pulmonary edema (HAPE) is not well understood. Ventilation and fluid-handling abnormalities at high altitude (HA) may play a role in HAPE. Because ventilatory and cardiopulmonary responses to chronic HA exposure in the Hilltop (H) strain of Sprague-Dawley rat are different from those in the Madison (M) strain, it was hypothesized that these strains would have different susceptibilities to developing HAPE. M and H rats were studied at sea level (SL) and in a hypobaric chamber after 9 and 12 h at a simulated altitude of 24,000 ft (barometric pressure = 295 mmHg) and 1, 12, and 24 h at a simulated altitude of 18,000 ft (barometric pressure = 380 mmHg). Both strains developed HAPE, but the M rat was more susceptible to HAPE, as demonstrated by a higher mortality rate from hemorrhagic pulmonary edema after 9 h at 24,000 ft and an earlier increase in lung water after exposure to 18,000 ft. Minute ventilation was similar in both strains at HA, but arterial PO2 was significantly higher in the M rat. Both strains had a significant decrease in fluid intake and negative sensible water balance at HA. No changes in plasma renin activity, aldosterone concentrations, antidiuretic hormone levels, and atrial natriuretic peptide levels were found at HA. The increased susceptibility of the M rat to HAPE is therefore not explained by ventilation or fluid-handling abnormalities.

Community-Acquired Acute Renal Failure

Acute renal failure usually occurs during hospitalization, but may also be present on admission to the hospital. To define the causes and outcomes of community-acquired acute renal failure, we undertook a prospective study of patients admitted to the hospital with acute elevations in serum creatinine concentrations. Over a 17-month period, all admission serum creatinine determinations were screened for patients with values greater than 177 δmol/L (2 mg/dL). These values were compared with baseline creatinines to select patients with an acute elevation in serum creatinine occurring outside the hospital. One hundred patients were entered into the study, with an overall incidence of 1% of hospital admissions. Seventy percent of the patients had prerenal azotemia, 11% had intrinsic acute renal failure, 17% had obstruction, and 2% could not be classified. Mean peak serum creatinine (318 ± 18 δmol/L [3.6 ± 0.2 mg/dL]) and mortality (7%) was lowest In the group with prerenal azotemia. In this group, volume contraction due to vomiting, decreased fluid intake, diarrhea, fever, glucosuria, or diuretics was the most common underlying cause. The group with Intrinsic acute renal failure had the most severe renal failure and the highest mortality (55%). Although ischemic acute tubular necrosis is the most common cause of hospital-acquired intrinsic acute renal failure, this etiology was seen in only one patient. Drug-induced nephrotoxicity and Infection-related causes were the most common underlying etiologies of intrinsic acute renal failure. Obstructive renal failure had a mortality of 24% and was most commonly due to benign prostatic hypertrophy. Almost 90% of the patients admitted to the hospital with an acute increase in serum creatinine concentration have a potentially reversible cause, either volume contraction or obstruction. Nevertheless, the overall mortality in these patients is 15%, and the risk of dying is increased in those patients with intrinsic acute renal failure and those with higher peak serum creatinine concentrations.

Identification of Feeding and Nutrition Problems in Young Children with Neuromotor Involvement

The purpose of this article is to provide information needed to identify feeding and nutrition problems in children from birth to twenty-four months. Oral-motor and self-feeding skill development should be viewed within the framework of overall development and changing nutrition needs. Neuromotor dysfunction affects feeding and nutrition through changes in muscle tone, reflexes and the response to sensory stimulation. Nutrient compromises, including delays in texture progression, decreased fluid intake, and problems associated with self-feeding and food selection must be considered when assessing the nutrition/feeding needs of children. Successful completion of the self-assessment can be used to check the reader's basic understanding of the subject.

Pharmacology of drug self-administration

Limited access to drugs provides a reliable model for their acute-reinforcing effects and a means by which to explore neuropharmacological mechanisms involved in these effects. In limited access situations intravenous self-administration rates of opiates and psychomotor stimulants is inversely related to dose, and competitive antagonists at low doses increase the number of injections self-administered. Competitive agonists decrease drug self-administration. However noncompetitive antagonists tend to produce decreases in self-administration and the specificity of these results are difficult to interpret. A limited access procedure of ethanol (10% v/v) self-administration using a sucrose or saccharin fade out procedure resulted in reliable and stable ethanol (10% v/v) and water self-administration in a concurrent choice situation using nondeprived unselected Wistar and alcohol preferring P-rats. As observed by others, the opiate antagonist naloxone decreased fluid intake in both strain of rats. However, contrary to earlier results naloxone did not produce a selective decrease in ethanol preference. The serotonin antagonist methysergide had no significant effect on fluid intake or ethanol preference. However, the long-acting dopamine agonist bromocriptine decreased ethanol intake and increased water intake producing a significant decrease in ethanol preference. The results with naloxone suggest that opiate interactions with ethanol may reflect a more general effect on consummatory behavior and the results with bromocriptine suggest that the reinforcing effects of low doses of ethanol may involve a dopaminergic component. Future studies should explore further the interactions of ethanol with competitive antagonists (if possible), and fluid intake or ethanol preference with limbic-extrapyramidal circuitry involved in mediating the reinforcing actions of other drugs of abuse.

Dietary modulation of the anorectic potency of amphetamine

The effects of intake of an amphetamine solution on food and fluid intakes, body weight (b.wt.) and feed efficiency (FE) were examined in rats fed either a high-carbohydrate (HC) (65% of total calories) or high-fat (HF) (65% of total calories) diet. During a 17-day predrug period, neither caloric intake, fluid intake, b.wt. nor feed efficiency (FE) differed as a function of diet. When given a 0.1 mg/ml amphetamine sulfate (AMPH) solution as their sole source of fluid, rats in both diet groups decreased fluid intake by an equivalent amount. While diet did not influence AMPH intake, it did alter the drug's effects on caloric intake, b.wt. and FE. In both diet groups, rats drinking AMPH decreased caloric intake, b.wt. gain and FE relative to rats which drank water. However, rats fed the HC diet decreased caloric intake less, but lost more weight than rats fed the HF diet. Further, rats fed the HC diet displayed a rapid tolerance to the anorectic effects of AMPH, with no tolerance to the drug's effect on b.wt. In contrast, rats fed the HF diet suppressed caloric intake throughout the drug period, but weighed more than rats fed the HC diet. Thus, when drinking the AMPH solution, FE of rats fed the HC diet was significantly lower than that of rats fed the HF diet. When the drug was removed, rats eating the HC diet failed to alter caloric intake and b.wt. In contrast, rats fed the HF diet increased caloric intake and gained weight. These data indicate that dietary factors must be considered when evaluating the anorectic actions of psychopharmacological agents.