Saline-infused Controls Research Articles

Effect of naloxone on oxytocin and vasopressin release during vaginocervical stimulation in the goat

We have investigated the secretion of oxytocin and arginine vasopressin (AVP) during vaginocervical stimulation in the conscious goat and examined the effect of the opioid antagonist naloxone on peptide release to this stimulus. Goats were implanted with guide tubes overlying the cisterna magna under anaesthesia and allowed to recover. Vaginocervical stimulation for 60 s resulted in a marked (P less than 0.01) release of oxytocin into the plasma but neither plasma AVP nor cerebrospinal fluid (CSF) concentrations of oxytocin changed significantly. In a second series of experiments, unoperated goats were infused with saline or naloxone (4 mg bolus + 12 mg/h) in random order on two separate occasions. Infusion of naloxone had no effect on basal plasma concentrations of oxytocin or AVP. There was a marked and significant (P less than 0.01) potentiation of oxytocin secretion following vaginocervical stimulation in animals infused with naloxone. Naloxone-infused animals showed a significant (P less than 0.01) rise in plasma AVP after stimulation but plasma AVP did not change in the saline-infused controls. We conclude that vaginocervical stimulation leads to the selective release of oxytocin from the neurohypophysis without affecting concentrations of oxytocin in the CSF. Endogenous opioids inhibit the stimulated secretion of oxytocin and AVP in vivo in response to vaginocervical stimulation in the goat.

Glucose infusion arrests the decompensatory phase of hemorrhagic shock.

Waning of hyperglycemia has been shown to be closely associated with the deterioration of mechanisms supporting homeostasis during hemorrhagic shock. However, the mechanisms which link plasma glucose levels to maintenance of homeostasis during hemorrhagic shock are not clear. The goal of the present study was to evaluate the importance of glucose to maintenance of compensatory mechanisms. This was undertaken by maintaining plasma glucose levels through infusion of hypertonic glucose (2-3 M) starting at the onset of decompensation during persisting hypovolemia. Administration of glucose at a rate of between 60 and 80 mumoles/min X kg arrested the fall in glucose concentration and significantly slowed or arrested the decompensatory phase. All of the saline infused control animals (n = 6) died within 3 hours after reaching their maximum shed blood volume, averaging 145 +/- 25 minutes, while two of the eight animals in the glucose infusion group died less than 4 hours after reaching the maximum shed blood volume. The remaining six animals were sacrificed between 270 and 397 minutes (average, 340 +/- 22 minutes) after reaching the maximum shed blood volume since decompensation was arrested. Compared to the saline-infused control group, animals receiving glucose infusion exhibited a more moderate acidosis, and the hemoconcentration which normally accompanies decompensation was also prevented. Since the increase in plasma osmolality and the fraction of the total osmolality change accounted for by glucose was less in the glucose-infused animals, these results suggest that the effect is not mediated through a glucose-related maintenance of a transcapillary osmotic gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic antagonist infusion does not increase morphine antinociception in rat spinal cord

Chronic spinal infusion of the opiate antagonist naloxone or naltrexone fail to influence the antinociceptive effect of subsequent intrathecal morphine on the hot plate test in rats compared to saline-infused controls. These results contrast the functional supersensitivity to morphine seen after long-term systemic opiate antagonist administration and support the hypothesis that dopaminergic interactions, lacking in the spinal cord, are necessary for antagonist-induced opioid receptor upregulation.

Effects of chronic infusion of porcine relaxin on oxytocin release in lactating rats.

The effects of chronic infusion of porcine relaxin on oxytocin release were studied in lactating rats. Infusion of relaxin (4.2 micrograms/h for either 4 or 6 days) suppressed reflex milk ejection and reduced litter weight gain for 48 h compared with saline-infused controls. After 2 days, neither the rate of growth nor the frequency of milk ejection were significantly different from controls. For 24 h after the infusion of relaxin ended, litters gained weight more quickly than controls but there was no difference seen in the frequency of milk ejection. The effects on oxytocin release of stopping an infusion of relaxin after 3 days were investigated. There was a significant (P less than 0.01) rise in plasma oxytocin (up to 90 pmol/l) 30 min after the infusion was stopped, followed by a sustained rise in intramammary pressure. Treatment of relaxin-infused rats with naloxone (0.1 mg/kg) when the infusion was halted caused a more rapid release of oxytocin (within 2 min), a greater release of oxytocin (up to 140 pmol/l) and a prolonged rise in intramammary pressure.

Intracellular chloride activity in intact rat liver: relationship to membrane potential and bile flow.

Active chloride transport has been described in a variety of epithelia, and intracellular chloride activity (aiCl) in these tissues is generally elevated twofold or more above the level predicted for passive diffusion. To determine whether active chloride transport might contribute to canalicular bile formation, we have used conventional and Cl- -selective microelectrodes to measure aiCl of rat hepatocytes in vivo under a variety of conditions. Under basal conditions, the membrane potential difference averaged -33.2 +/- 3.5 mV (means +/- SD) in 29 animals, and the ratio (R) of observed aiCl (24.8 mM) to that expected for passive distribution at this membrane potential (22.6 mM) was 1.10 +/- 0.08, a value slightly but significantly greater than that predicted for passive distribution. Infusion of alanine (45-mumol bolus, 10.8-mumol/min infusion) in 5 animals hyperpolarized the membrane potential to -43.6 +/- 4.0 mV over 10-15 min and resulted in a significant fall in aiCl to 15.1 +/- 4.8 mM but with no change in R. Infusion of theophylline (577 nmol/min), taurocholate (3-mumol bolus, 810-nmol/min infusion), and ursodeoxycholic acid (4-mumol bolus, 2.13-mumol/min infusion) into 5 animals each increased bile flow by 6.1, 34.1, and 96.8%, respectively, compared with saline-infused controls but did not alter membrane potential or chloride distribution. These observations indicate that aiCl is close to the level predicted for passive distribution under basal conditions, after hyperpolarization of the membrane potential by alanine, and after stimulation of bile flow by a variety of choleretics. By analogy with Cl- -secreting epithelia, it appears unlikely that active chloride transport across the basolateral membrane contributes significantly to canalicular bile formation by the hepatocyte.

Mechanical factors regulating gastric emptying examined by the effects of exogenous cholecystokinin and secretin on canine gastroduodenal motility.

The aim of this study was to elucidate the variables of gastroduodenal motility determining gastric emptying. For this purpose the effects of exogenous cholecystokinin, secretin, and gastric inhibitory polypeptide on motility and gastric emptying were studied during a meal. Motility was measured with extraluminal strain gage force transducers and induction coils in unanaesthetized dogs. The pyloric diameter and the duodenal lumen were evaluated from radiographs. Gastric emptying of an acaloric cellulose meal was determined radiographically. When compared with control infusion of saline, cholecystokinin (1.7 Ivy units X kg-1 X h-1) and secretin (1.7 clinical units X kg-1 X h-1) delayed gastric emptying and diminished the force of the antral contractions, the force and frequency of the duodenal contractions, and opening of the pylorus. The contractile patterns of the duodenum were changed from propulsive to segmenting activity. Cholecystokinin additionally diminished the duodenal lumen. In contrast, gastric inhibitory polypeptide (1.5 microgram X kg-1 X h-1) did not influence gastroduodenal motility and gastric emptying. It is concluded that the motility parameters that were significantly altered by cholecystokinin and secretin are involved in the control of gastric emptying, while other parameters that remained unchanged play a minor role in the regulating process.

Confirmation of the inhibitory influence of exogenous oxytocin on cortisol and ACTH in man: evidence of reproducibility.

The influence of low-dose oxytocin perfusion (32 mIU/min) on ACTH and cortisol plasma levels was tested in 8 normal male volunteers (age 18-26). The 1-h oxytocin perfusion periods were preceded and followed by two 1-h saline control periods. During the first period, there was a slight ACTH concentration decrease in 4 individuals. Oxytocin perfusion induced a clear-cut plasma ACTH decrease in 7 out of the volunteers, and a slight decrease in the remaining one. During the second saline infusion, there was a marked ACTH increase in 7 out of the volunteers, and a weak increase in one (P less than 0.0001). A similar pattern was observed in the plasma cortisol levels (P less than 0.00001). Furthermore, a control saline perfusion was performed in 4 of the 8 volunteers and compared to the 4 corresponding oxytocin perfusion tests: the differences between the 2 sets of tests was highly significant both for ACTH (P less than 0.003) and for cortisol (P less than 0.007). Lastly, the reproducibility of this inhibitory influence was retested in 4 volunteers: the tests were repeated under the same conditions 7 days later. There were no global differences between the 2 sets of tests either for ACTH (NS) or for cortisol (NS). ACTH and cortisol concentration fluctuations during the period between each set of tests were not significant. The following variations were measured for ACTH (NS) and for cortisol (NS). The present results confirm the inhibitory influence of low-dose oxytocin perfusion on ACTH and cortisol levels in normal males.(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue-specific concentration changes of estrone and estradiol during spontaneous and ACTH-induced parturition in sheep.

Changes in estrogen production are considered important in the sequence of events leading to parturition. We sought tissue-specific changes in the concentration of unconjugated estrone (E1) and estradiol (E2) in intrauterine fetal (amnion, chorion) and maternal (endometrium, myometrium) tissues during normal pregnancy, labour, and ACTH-induced labour in sheep. The mean concentrations of E1 and E2 in the fetal membranes were higher than in endometrium and myometrium. In amnion there were no consistent changes in estrone concentrations with gestation, although estradiol concentrations increased between day 130 and term. In the endometrium there were increases in both estrone and estradiol between day 100 and term, whereas in the myometrium increases in the concentrations of E1 and E2 occurred between days 130-135 and term. Animals showing a labourlike pattern of uterine contractions after intrafetal ACTH administration did not show significant differences in estrone or estradiol concentrations in amnion, chorion, or endometrium compared with saline-infused controls. However, there was a progressive increase in the concentration of estrone and estradiol in the myometrium during ACTH-induced labour. We conclude that changes in the concentrations of estrone and estradiol in intrauterine tissues vary between the tissues studied and the two estrogens. In general, estrogen concentrations increased towards term, but this trend was more marked in the maternal than fetal tissues. The changes in estrone concentrations in myometrium, but not in the other tissues, were replicated during ACTH-induced labour. Our results would be compatible with the suggestion that tissue-specific changes in estrogen concentrations may contribute to the local intrauterine steroid milieu during pregnancy and at term.

Intraventricular insulin reduces food intake and body weight of lean but not obese zucker rats

Porcine insulin (2 mU/rat/day) and its saline vehicle were infused into the third cerebral ventricle of female lean or obese Zucker rats using 14-day osmotic minipumps. Lean rats receiving saline (N = 6) gained 14 +/- 3 g over the 14 days, whereas lean rats receiving insulin (N = 7) lost 12 +/- 4 g over the same interval (p less than 0.01). The average total food intake of the insulin-infused group was decreased by 14% (p less than 0.05) as compared with that of the saline-infused group. The decreased caloric consumption was adequate to account for the body weight loss. Insulin infusion had no effect on food intake or body weight of the obese rats relative to their saline-infused controls (change in body weight: saline (N = 5), -14 +/- 23 g; insulin (N = 7), +3 +/- 14 g). These results suggest that genetically obese Zucker rats have reduced sensitivity to insulin in the central nervous system. We propose that this phenomenon may participate in the development and maintenance of hyperphagia and obesity in these animals.

Pulsatile administration of gonadotropin-releasing hormone advances ovulation in cycling mares.

Cycling standardbred mares were infused with saline or 20 micrograms gonadotropin-releasing hormone (GnRH) in a pulsatile pattern (one 5-sec pulse/h, 2 h or 4 h) beginning on Day 16 of the estrous cycle. Although serum concentrations of luteinizing hormone (LH) increased significantly earlier in all three GnRH-treated groups (within one day of the initiation of infusion) compared to saline-infused controls, there were no differences in peak periovulatory LH concentrations among treatments (overall mean +/- SEM, 8.98 +/- 0.55 ng/ml). The number of days from the start of treatment to ovulation was significantly less in mares infused with 20 micrograms GnRH/h (mean +/- SEM, 2.9 +/- 0.6 days after the initiation of treatment, or 18.9 days from the previous ovulation; N = 7) compared to mares treated with saline (5.9 +/- 0.3 days, or 21.9 days from previous ovulation; N = 7) or 20 micrograms GnRH per 4 h (5.4 +/- 0.9 days or 21.4 days from previous ovulation; N = 5). Although mares infused with 20 micrograms GnRH/2 h ovulated after 4.3 +/- 0.7 days of treatment (Day 20.3; N = 7), this was not significantly different from either the control or 20 micrograms GnRH/h treatment groups. Neither the duration of the resulting luteal phase nor the length of the estrous cycle was different between any of the treatment groups (combined means, 14.7 +/- 0.2 days and 21.3 +/- 0.4 days, respectively). We conclude that pulsatile infusion of GnRH is effective in advancing the time of ovulation in cycling mares, but that the frequency of pulse infusion is a critical variable.

Short-term control of feeding: Limitation of the glucostatic theory

In the rat, the short-term effect on spontaneous feeding of intravenous administration of either glucose or glucose plus insulin was investigated. The infusions lasted 4 hours and covered 170% of rats's previously measured spontaneous caloric intake, while control infusions of saline and saline plus insulin were also made. Feeding patterns in subjects' home cages were recorded. Glycaemia and glycosuria were measured in order to asses glucose utilization. When it was infused alone, glucose was utilized at 95% and so covered 160% of oral caloric requirements, while the reduction of oral intake was only 40%. When insulin was co-infused with glucose, utilization reached 100% and oral feeding was reduced by 70%. Saline infusions did not affect oral feeding and insulin brought about the expected increase in feeding. It is proposed that the mechansim which sustains feeding should depend on multiple macronutrients utilization rather than on one specific chemical family. Furthermore, the fact that insulin has a clear-cut effect, despite its lipogenetic, i.e., metabolite-sequestering properties, favors the ischymetric hypothesis (based on cellular power-production), rather than the energostatic one (based on yields of nutrients).

Effects of naloxone on renal responses to noxious stimuli in the cynomolgus monkey

Behavioral influences on excretion of Na+ and H2O were studied during saline diuresis in three unanesthetized adult female cynomolgus monkeys. During control infusions of isotonic saline, the average rates of urine and Na+ excretion were 210µl/kg/min and 36.1µl/kg/min, respectively, and the average rate of inulin clearance was 4.6 ml/kg/min. Intermittent exposure to an electrical stimulus applied to the monkey's tail for a 30-min period modestly reduced rates of excretion of Na+ and H2O; these reductions were 58% and 56% of baseline values respectively during the first 10 min, but excretion rates returned to baseline values or exceeded them by the end of the 30-min period. The effects of naloxone hydrochloride (10 mg/kg), an opiate antagonist, were studied by administering the drug immediately before the period of electrical-stimulus delivery. After naloxone, the electrical-stimulus markedly reduced the rates of Na+ and H2O excretion to 29% and 31% of baseline values during the first 10 min, and delayed the return to baseline values. Inulin clearance was not altered significantly by the electrical stimulus in the absence of naloxone, but was decreased to 32% of the baseline rate during the first 10 min of exposure to the electric stimulus in the presence of naloxone. Naloxone had similar effects on rates of Na+ and urine excretion in response to 30 min of 108 dBA noise. These results show that renal responses to noxious environmental stimuli (electrical stimulus or noise) can be altered by naloxone.

Effect of CCK-8 on basal and meal-stimulated somatostatin in the baboon

We measured the ability of CCK-8 alone, a test meal alone, or a combination of the two, to increase peripheral plasma somatostatin levels in the baboon. Baboons received a five-minute intravenous infusion of either CCK-8 (1, 2, or 4 μg/kg) or saline prior to a 30-minute meal. CCK-8 administration at all doses resulted in a significant rise of plasma somatostatin-like immunoreactivity (SLI). In addition, ingestion of a meal following a control saline infusion resulted in a significant rise of plasma SLI. However, the meal-related rise in SLI was blunted by prior administration of CCK-8 at all doses, including a dose which did not significantly decrease meal size. CCK-8 administration at all doses also blunted the meal-related rise of plasma insulin and glucose. We conclude that the known ability of CCK-8 to inhibit gastric emptying, as well as to decrease meal size, may account for its suppression of the meal-related SLI release.

Epinephrine is not critical to prevention of hypoglycemia during exercise in humans.

We documented stability of plasma glucose concentrations and glucose production and utilization rates, and levels of other metabolic substrates and regulatory factors, during the islet clamp (somatostatin infusion with glucagon and insulin replacement) in the absence of an intervention in five normal humans and further applied this technique to the study of glucoregulation during moderate exercise. Based on previous evidence that sympathochromaffin activation plays a primary role in the prevention of hypoglycemia during exercise, the role of adrenomedullary catecholamines was assessed by exercise (60% of maximum oxygen consumption for 60 min) studies in four bilaterally adrenalectomized, epinephrine-deficient humans under two conditions: control (saline infusion) and islet clamp. Increased glucose utilization and production rates were matched and plasma glucose was unchanged during exercise under both conditions. Thus adrenomedullary catecholamines including epinephrine are not critical to glucoregulation during moderate exercise in humans even when changes in insulin and glucagon are prevented. These findings provide further support for the suggestion that sympathetic neural norepinephrine is the operative catecholamine in the prevention of hypoglycemia during exercise in humans.

Epidermal growth factor: effect on circulating thyroid hormone levels in sheep.

Observations on the effect of thyroid hormones on mouse submaxillary gland epidermal growth factor (EGF) and on the complementary effect of EGF on cultured thyroid cells led us to examine the interaction between EGF and thyroid hormones in the whole animal, during and after 24 h of infusion of 3.3 micrograms/kg X h mouse EGF into 6 merino ewes. There was a profound depression of both circulating T4 and T3 levels, to less than 20% of saline-infused control values, extending beyond the end of infusion. Plasma TSH concentrations were unchanged during the first 8 h of the infusion, excluding the likelihood of a suppressive effect of EGF on the hypothalamic-pituitary axis. Serum rT3 and 3,3'-diiodothyronine, however, experienced a more transitory 6-fold increase. These findings are consistent with a dual inhibitory effect of EGF on both thyroid hormone secretion and peripheral metabolism.

Dual effect of morphiceptin on lordosis behavior: Possible mediation by different opioid receptor subtypes

Intracerebroventricular (ICV) infusions of the selective μ receptor agonist morphiceptin produce a dual effect on lordosis behavior in ovariectomized, steroid-primed rats. Low doses of morphiceptin (20 ng) inhibit lordosis whereas higher doses (2000 ng) facilitate this behavior. The present experiment tested whether naloxone, an antagonist of both high- and low-affinity μ receptors, or the long-acting high-affinity μ receptor antagonist naloxazone could block the dual effect of morphiceptin on lordosis. Ovariectomized rats primed with estrogen and progesterone received naloxone, naloxazone, or a control solution prior to ICV infusions of either 0, 20, or 2000 ng of morphiceptin. Naloxone reversed both the inhibition and facilitation of lordosis produced by morphiceptin, but had no effect on lordosis when administered before control infusions. In contrast, naloxazone reversed the inhibition but not the facilitation of lordosis. These results indicate that the inhibitory effect of morphiceptin on lordosis reflects the activation of high-affinity μ receptors whereas the facilitatory effect reflects either the activation of low-affinity μ receptors or other opioid receptor subtypes. The failure of naloxone or naloxazone to affect lordosis in rats receiving control infusions of saline further suggests that endogenous opioid systems do not exert a tonic inhibitory or facilitatory action on lordosis behavior.

Effects of timed melatonin infusion on prolactin secretion in pineal denervated goat.

The effects of timed melatonin infusion on prolactin secretion were examined in the pineal denervated goat. Ovariectomized Shiba goats (n = 5) were subjected to bilateral superior cervical ganglionectomy (SCGX); this procedure resulted in complete abolition of endogenous melatonin release during the dark phase. SCGX goats failed to coordinate their prolactin secretion with the prevailing photoperiod. Melatonin was infused (20 micrograms/h, s.c.) daily into these goats either for 8 h (the long-day-type infusion) or for 16 h (the short-day-type infusion) to mimic the nocturnal profile of plasma melatonin under long days or short days, respectively. The long-day-type melatonin infusion for 9 days, in comparison with control saline infusion, accelerated prolactin secretion, inducing a nocturnal rise in plasma prolactin; this was comparable to that seen in the pineal intact goats under long photoperiods. On the other hand, the short-day-type melatonin infusion suppressed prolactin secretion throughout the day as the short-day treatment did in intact goats. The prevailing photoperiod appeared to have no distinct effect on these prolactin responses to exogenous melatonin, which were indistinguishable under 16L8D and 8L16D conditions. The results indicate that the information about external light-dark cycles is converted by the pineal gland into the endocrine signal as a daily pattern of melatonin secretion, which eventually regulates prolactin secretion from the pituitary gland of the goat.

Evidence that opioid peptides and dopamine participate in the suckling-induced release of prolactin in the ewe.

A pharmacological approach was used to study the involvement of opioid peptides and dopamine in mediating the suckling-induced release of prolactin in the lactating ewe (10-20 days post partum). To promote reliable and predictable suckling activity lambs were fitted with elasticated masks to prevent sucking for 4.5 h. After a 1-hour control period of frequent blood sampling, ewes were treated (i.v. injections every 5 min) for a further 75 min with either saline vehicle, an opioid antagonist (naloxone; 4.17 mg/5 min), a dopamine antagonist (metoclopramide; 1.25 mg/5 min), a mixture of naloxone + metoclopramide or a dopamine agonist (apomorphine; 6.6 mg/5 min). Blood was withdrawn at 5-min intervals for determination of plasma prolactin and luteinizing hormone (LH) by radioimmunoassay. Plasma LH concentrations (less than or equal to 1 microgram/l) were not significantly affected by any of the drug treatments and there was no evidence for an acute fall in LH associated with suckling- or TRH-induced increases in prolactin secretion. Naloxone significantly (p less than 0.05) reduced the mean incremental change in prolactin concentration (delta PRL) in response to suckling (+7 +/- 18 micrograms/ml) compared with saline-infused controls (+79 +/- 26 micrograms/ml), an effect which was completely reversed by combined treatment with naloxone and metoclopramide (+146 +/- 56 micrograms/ml). Metoclopramide alone raised basal prolactin levels by 46% (p less than 0.01) but did not affect delta PRL in response to suckling (+115 +/- 52 micrograms/ml). Neither naloxone, metoclopramide nor a combination of the two drugs affected the subsequent prolactin to TRH (10 micrograms). Apomorphine, however, completely abolished both the suckling- and TRH-induced release of prolactin.(ABSTRACT TRUNCATED AT 250 WORDS)

Normal lactotroph sensitivity to graded low-dose dopamine infusions in pathological hyperprolactinemia.

The question as to whether there is lactotroph resistance to dopamine (DA) in pathological hyperprolactinemia (PHP) is unresolved. Previous studies utilizing low-dose DA infusions to study lactotroph function have not considered the diurnal changes in prolactin (PRL) secretion that occur in normals but which are lost in PHP. As PRL levels show a fall in the hours after waking, studies performed during this time of day will falsely show a greater fall of PRL in normals than in PHP patients. The aim was to readdress the issue of lactotroph sensitivity using a study designed to minimize the problem arising from diurnal PRL changes. Eight normal subjects, 17 patients with PHP, and 6 hyperprolactinemic patients with nonfunctioning pituitary tumors (NFTs) were studied with three graded doses of DA - (0.01, 0.05, and 0.5 micrograms/kg X min) - by relating the changes induced by each dose to the maximal spontaneous fall in PRL that occurred during a 3-hour control saline study. The mean +/- SE maximal fall in PRL during control saline infusion to 46.0 +/- 4.1% of basal in normal subjects was significantly greater (p less than 0.001) than the fall in patients with PHP (88.0 +/- 1.0%) or NFTs (87.5 +/- 2.6%). The apparent fall in PRL was significantly greater in normals during the two lower infusion doses, but not at the highest dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of Progesterone-Induced Gonadotropin Surge by Adrenergic Agonists in Estrogen-Primed Ovariectomized Rats

An involvement of catecholamines in the preovulatory gonadotropin surge has been proposed for many years. Specifically, an alpha-adrenergic mechanism has been implicated in the stimulation of ovulation and LH release. On the other hand, little is known regarding the possible role of adrenergic neurotransmission once a gonadotropin surge has been initiated. In this study, drugs which affect adrenergic receptors were administered centrally to estrogen-primed ovariectomized rats and the effects on serum concentrations of LH and FSH induced by treatment with progesterone at 08:00 h were examined. As expected, the progesterone treatment caused a significant (p less than 0.05) increase in blood LH and FSH levels by 14:00 and 15:00 h, respectively, when compared with those seen at 13:00 h. In control rats that received isotonic saline intraventricularly at 15:00-16:00 h, both LH and FSH levels continued to rise linearly and reached peak levels by 17:00 and 18:00 h. By contrast, intraventricular infusion of norepinephrine at 16:00 h caused a significant decrease (p less than 0.05) in LH levels when compared with the saline-infused control groups. Moreover, rats that received intraventricular infusion of phenylephrine (an alpha 1-adrenergic agonist) at 15:00 h failed to show a significant increase in LH and FSH levels until 19:00 h; this inhibitory effect was mimicked by a relatively more specific alpha 1-adrenergic agonist, methoxamine. Consistent with our previous findings, animals which received intraventricular isoproterenol (a specific beta-adrenergic agonist) at 15:00 h also responded with suppressed serum LH levels at 16:00-19:00 h when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)