The differences in feeding-inhibitory responses to peripheral and central leptin between non-lactating and lactating rats.

This study was conducted to examine the contributions of central and peripheral leptin to hyperphagia in lactation. Lactating rats were mated at 7-8 weeks of age and housed singly with their litters. In experiment 1, food intakes were significantly (P<0.01) greater (350% on average) in lactation than in non-lactation throughout a day. Cerebrospinal fluid (CSF) leptin levels remained constant despite plasma leptin levels being significantly (P<0.05) greater in non-lactation than in lactation. In experiment 2, CSF leptin levels were not altered by i.v. injections of leptin (0.2 and 0.4 mg/kg body weight) despite that plasma leptin levels were dose dependently (P<0.01) increased. Moreover, i.v. administration of leptin significantly (P<0.05) decreased food intake in non-lactating rats but not in lactating rats. In experiment 3, nocturnal food intakes were temporarily (P<0.05) reduced in non-lactating and lactating rats. I.c.v. administration of a leptin antagonist (15 µg) blocked the reductions of food intakes. I.c.v. administration of leptin (10 µg) significantly (P<0.05) decreased cumulative food intakes during 24 h in both the physiological states. In conclusion, this study has presented new evidence that the hyperphagia of lactating rats could be partly due to depressed sensitivity of neurons contacting blood leptin. In contrast, the responsiveness of leptin receptors contacting CSF leptin may not differ between non-lactating and lactating rats. Furthermore, the levels of CSF leptin remained constant independent of those of blood leptin. Therefore, the expression of hypothalamic leptin receptors contacting CSF could be involved in the difference in food intake between non-lactating and lactating rats.

Effects of age on cerebrospinal fluid oxytocin levels in free-ranging adult female and infant rhesus macaques.

There is growing interest in examining oxytocin and social functioning in human and non-human primates. Studies of human oxytocin biology are typically restricted to peripheral assessments because opportunities to collect cerebrospinal fluid (CSF) are rare. Several studies have examined CSF oxytocin levels in captive adult primates, but none to our knowledge have been conducted under free-ranging conditions and inclusive of infants. The main goal of this study was to establish feasibility of quantifying CSF oxytocin levels in free-ranging adult female and infant rhesus monkeys living on Cayo Santiago, PR. CSF oxytocin levels were examined in relation to individuals' demographic and reproductive characteristics as well as plasma cortisol levels. CSF oxytocin concentrations ranged from 36.02 to 134.41 pg/ml in adult females (ages 7-26 years; N = 31) and 35.94 to 77.3 pg/ml in infants (ages 38-134 days; N = 17). CSF oxytocin levels were positively correlated with adult female age and negatively correlated with infant age. The former correlation was driven by reproductive status. CSF oxytocin levels were unrelated to dominance rank or plasma cortisol levels. In contrast to a previous study of plasma oxytocin concentrations in this population, CSF oxytocin levels did not differ significantly between lactating and non-lactating females. These findings: 1) provide feasibility data for examining CSF oxytocin levels in free-ranging non-human primates and 2) indicate that CSF oxytocin levels may be a biomarker of age-related central nervous system changes across lifespan development. Research is now required to examine CSF oxytocin levels in the context of social functioning in free-ranging rhesus monkeys.

Pulses of oxytocin in the cerebrospinal fluid of rhesus monkeys.

Cerebrospinal fluid (CSF) samples were collected at frequent intervals (every 10-15 min) to determine if oxytocin pulses were present in the CSF of monkeys. Temporary indwelling subarachnoid catheters, with the tip of the catheter at the T12-L1 subarachnoid space, were placed in 4 nonlactating and 3 lactating (4 months post partum) female monkeys. Monkeys were maintained on jacket/tether/swivel systems in a constant photoperiod (07.00-19.00 h). CSF was continuously withdrawn at a rate of 1.2 ml/h by peristaltic pump, and CSF was collected in 15-min fractions (from 3 lactating monkeys and 1 nonlactating monkey) or in 10-min fractions (from the other 3 nonlactating monkeys) using a fraction collector. CSF oxytocin was measured by radioimmunoassay. Pulses of oxytocin were analyzed using the computerized Pulsar pulse detection algorithm. A pulsatile pattern of oxytocin concentrations was found in the CSF of lactating and nonlactating monkeys. The ultradian pulses of oxytocin were superimposed upon the diurnal rhythm of oxytocin in CSF. We conclude that frequent sampling of CSF provides a way to monitor moment-to-moment changes in central nervous system concentrations of oxytocin in primates.

Role of cholecystokinin in feeding and lactation.

The aim of this investigation was to study the release of cholecystokinin (CCK) in connection with feeding and lactation and to investigate the involvement of CCK in the regulation of food intake. For this purpose a method based on high performance liquid chromatography and subsequent radioimmunoassay (RIA) for the determination of CCK in plasma was developed. CCK was also determined in the cerebrospinal fluid (CSF) by RIA and is referred to as CCK-like immunoreactivity (CCK-LI). Different molecular forms of CCK in dog and rat plasma have been determined. These were found to differ from those in the CSF, suggesting that the CCK measured in plasma and CSF are derived from different sources, i.e. the gut and brain. CCK was released into plasma in response to feeding in dogs and rats and in response to suckling in lactating animals. The release of CCK is under vagal control. Thus, electrical vagal stimulation of anaesthetized rats increased plasma levels of CCK, and abdominal vagotomy abolished the suckling-induced release of CCK. Lesions of the lateral midbrain, which disrupt the oxytocin-mediated milk-ejection reflex, were also found to block the increase in plasma CCK in response to suckling. Intraperitoneal (i.p.) injection of CCK octapeptide (CCK-8) decreased food intake in food deprived male rats in doses which resulted in plasma concentrations within the physiological range. Intracerebral, but not i.p., injection of a low dose of a CCK antagonist, reversed the effect of peripheral CCK-8 on food intake as did i.p. injection of peripheral CCK A receptor antagonists. Thus, the mechanism by which i.p. CCK-8 inhibits food intake may involve both peripheral and central CCK receptor mechanisms. The concentration of CCK-LI in the CSF decreased after food deprivation and increased after feeding or i.p. CCK-8. Intraperitoneal injection of peripheral CCK antagonists prevented the increase in CCK-LI in the CSF and the inhibitory effect of i.p. CCK-8 on food intake. These data indicate that peripheral CCK receptor mechanisms induce a release of CCK in the brain. During the hyperphagia of lactation, plasma but not CSF levels of CCK were increased in the rat. Food deprivation markedly decreased the concentration of CCK in plasma and CSF; and the levels were restored in CSF, but not in plasma, after 1 h of feeding. Removal of the litter decreased food intake and increased the concentration of CCK in the CSF, but not in plasma. Lactating rats were less sensitive to the inhibitory effect of i.p.(ABSTRACT TRUNCATED AT 400 WORDS)

Offspring control of cerebrospinal fluid GABA concentrations in lactating rats.

The concentrations of gamma-aminobutyric acid (GABA) and its metabolic precursors glutamate (Glu) and ornithine (Orn) were measured in cerebrospinal fluid (CSF) samples obtained from the cisterna magna of freely moving lactating rats on: postpartum day 5 when the rats were with their pups, day 6, 6 h after removal of the pups, and day 7, 24 h after mother-pup reunion. The concentration of GABA was non-detectable in the absence of pups (condition 2) but forty-fold above the limit of detection whenever the rats and the pups were together (conditions 1 and 3). Glu and Orn were low in but increased in and still more so in. Thus, the CSF concentration of GABA, an inhibitory neurotransmitter which profoundly influences behavior and hormone secretion is markedly increased by the pup-related stimuli, which control the behavior and the endocrine secretions of the lactating rat.