Angiotensin-converting enzyme in subfornical organ mediates captopril-induced drinking.

These experiments tested whether angiotensin-converting enzyme (ACE) located within the subfornical organ (SFO) participates in the generation of water intake during peripheral ACE blockade with captopril (CAP). Lesions of the SFO virtually abolished drinking in response to intraperitoneal CAP injection. Intracranially injected CAP suppressed drinking induced by intraperitoneal CAP more completely with direct SFO injection compared with intraventricular or control tissue injections. This central captopril treatment did not alter the drinking response to subcutaneous hypertonic saline. Intraventricular injections of the angiotensin II (ANG II) receptor blocker sarile reduced drinking during oral captopril treatment in rats rehydrating from water deprivation. The results indicate that (a) the SFO mediates drinking caused by peripheral ACE inhibition; (b) the ACE located within the SFO may locally convert ANG I to ANG II, which then stimulates thirst; and (c) central ANG II receptors mediate thirst caused by peripheral ACE inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential neuronal responses to angiotensin III from the subfornical organ of normotensive and spontaneously hypertensive rats

We previously reported that chronic central administration of angiotensin III (AIII) fails to produce sustained drinking behavior in spontaneously hypertensive rats (SHR), possibly because of the development of early desensitization of the angiotensin receptors. The present study extended these findings to the cellular level, using brain-slice preparation from Wistar-Kyoto rats (WKY) and SHR, in conjunction with single-neuron recording in the subfornical organ (SFO), a target site for angiotensin II-induced drinking. We found that a majority of the SFO neurons studied (13/18 in WKY, 20/28 in SHR) responded in a dose-related manner to AIII, given in the range of 10(-6)-10(-5) M. This excitation was receptor-specific, since it was reversed by Ile7-AIII (10(-4)-10(-3) M), the selective AIII antagonist. Bestatin (10(-5)-10(-4) M), an aminopeptidase B inhibitor, did not discernibly affect basal spike frequency when delivered alone. Nevertheless, given in combination with the heptapeptide, bestatin reduced the intensity and duration of SFO neuronal response in WKY to the higher dose (10(-5) M), and in SHR to both doses (10(-6) or 10(-5) M), of AIII. These data suggest that the SFO may also be a central site of action for AIII. Moreover, prolonging the action of AIII by protecting it from being metabolized with bestatin may produce desensitization of the angiotensin receptors on SFO neurons. This was particularly so in the SHR, which are thought to be defective in the degradation of the heptapeptide in the brain.     

Interaction of hydration and subfornical organ lesions in sodium-depletion induced salt appetite.

The authors tested whether the level of hydration after furosemide diuresis and 22 hrs of sodium depletion affects the amount of water or 0.3 M NaCl solution consumed by rats with intact brains or with lesions of the subfornical organ (SFO). Rats received 2 (underhydrated) or 10 (euhydrated) ml/kg water by gavage as the only fluid input 2, 4, and 20 hrs after 10 mg/kg furosemide. These hydration treatments had little or no effect on the amount of saline consumed in 2 hrs by intact rats. SFO lesions reduced water intake regardless of hydration condition. Euhydrated, SFO-lesioned rats drank a normal amount of saline, but underhydrated, lesioned rats drank less saline than any other group. Thus, euhydration may facilitate salt appetite in SFO-lesioned rats, and the deficits in salt appetite noted in SFO-lesioned rats may result from deficits in water ingestion rather than from a destruction of angiotensin II receptor sites that directly provoke salt appetite. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long duration pressor responses following activation of subfornical organ neurons in rats are the result of increased circulating vasopressin

Electrical stimulation in the subfornical organ (SFO) of male Sprague-Dawley rats resulted in biphasic increases in blood pressure (BP) without a change in heart rate. The initial short duration (0-10 s) increase in BP lasted throughout the 10 s stimulation period (area under the curve (AUC) = 104.3+/-15.26 mmHg/s, (mean+/-SEM) P < 0.001). Upon termination of the electrical stimulus, the BP remained elevated for approximately 55 s (long duration response, AUC = 327.5+/-48.22 mmHg/s, P < 0.001). This long duration BP response was determined to be the result of an increase in circulating vasopressin (VP) as administration of a V1 receptor antagonist abolished this response (AUC = -210.7 +/- 42.38 mmHg/s, P < 0.01). The results of the present study demonstrate that the long duration component of the biphasic increase in BP observed on response to electrical stimulation of the SFO is the result of increased concentrations of circulating VP.     

Localization of receptors for the dipsogenic action of angiotensin II in the subfornical organ of rats.

Investigated the proposal that the subfornical organ (SFO) is a site of receptors for drinking induced by angiotensin II (AII). A total of 159 male albino Holtzman rats was used. Intracranial injections of physiological doses of AII elicited drinking if and only if applied directly to the SFO (Exp I). Ablation of the SFO selectively (Exp II) and permanently (Exp IV) eliminated drinking elicited by physiological doses of iv infused AII. Animals in which SFO had been ablated responded normally to cellular dehydration but reduced responding to the extracellular thirsts of beta-adrenergic activation and hyperoncotic colloid dialysis (Exp III). Infusion of saralasin, an AII antagonist, directly into the SFO selectively and reversibly antagonized iv AII drinking (Exp V). The hypothesis that the SFO contains dipsogenic receptors for circulating AII was supported. (2 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Atrial natriuretic peptide in the subfornical organ reduces drinking induced by angiotensin or in response to water deprivation.

Three experiments tested whether the subfornical organ (SFO) could be a site of action for the antidipsogenic effects of atrial natriuretic peptide (ANP) in rats. Pretreatment with 100, 230, or 500 pmol ANP in the SFO reduced drinking induced by 10 pmol angiotensin II in the SFO. Drinking in response to water deprivation was reduced by ANP in rats having cannulas in or near the SFO, but not in rats having cannulas distant from the SFO or in the ventricles. Finally, ANP had no effect on eating or drinking after food deprivation, suggesting that the rats in the other experiments were not acutely incapacitated. The SFO may mediate the central effects of ANP on drinking induced by angiotensin or in response to water deprivation and could play a similar role in the central effects of ANP on salt appetite, diuresis, vasopressin secretion, and blood pressure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regional differences in the morphology of the rat subfornical organ

Properties of whole milk and milk fractions from cows fed a diet that gave a greatly increased proportion of unsaturated fatty acid residues (especially of linoleic acid) in the milk lipids were studied, and this milk (high-linoleic milk) was compared with milk from cows on a control diet (control milk). The milk fractions were isolated by high-speed centrifugation of whole milk or cream and were examined by chemical analysis and electron microscopy. During centrifugation the globules of milk fat were disrupted and the membranes (fat-globule 'ghosts') floated as a layer beneath the free lipid. Membrane proteins from the 2 sorts of milk gave the same electrophoretic pattern and the amino acid compositions were the same. Lipid analysis of the membrane fraction from high-linoleic milk showed the expected increase in the proportion of unsaturated fatty acid residues in the neutral lipids, but there was an unexpected decrease in the proportion of unsaturated residues in the membrane phospholipids. No differences were found between high-linoleic and control milk in the ultrastructure of the milk-fat globules or the isolated membranes.     

Subfornical organ connectivity and drinking to captopril or carbachol in rats.

These experiments were conducted to test whether drinking to ip captopril or to intraventricular carbachol requires an intact fiber system from the ventral subfornical organ (SFO). Wire-knife cuts were made through the wall of the third ventricle ventral to the SFO. Control rats had either sham lesions or histologically identified missed cuts. Rats with good cuts (a) drank less than either control group after ip injections of 4 mg/kg captopril, (b) drank normal amounts of 0.3 M NaCl solution when captopril was placed in the drinking water at 0.1 rag/ml, (c) drank less water but a normal amount of saline after 6 mg/kg captopril ip and 10 mg/kg furosemide diuretic ip, and (d) drank normal amounts of water after lateral ventricular injections of 1.2 or 4 nmol of carbachol. The results of the captopril experiments confirm predictions based on studies of SFO lesions and suggest that captopril causes water, but not saline, drinking via an angiotensin-related mechanism acting at the SFO. The carbachol experiment indicates either that the SFO is not a unique receptor site for ventricular carbachol or that the fibers mediating this response do not require the pathways through the ventral pole of the SFO. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Peptide and acetylcholine action on neurones of the cat subfornical organ

This paper presents evidence for an IgG1 allotype detected by a sheep antibovine serum. The character which appears to be inherited in a simple Mendelian way has been named G1a1.     

Effects of subfornical organ extracts of salt-water balance in the rat

The subfornical organ (SFO) is regarded as a neurosecretory structure but no information is available on the nature or biological effects of the secretory products(s). Supernatants of water homogenates of rat SFO were lyophilized and reconsittuted in artificial cerebrospinal fluid (CSF). Intracerebroventricular (IVT), but not subcutaneous, administration of this material to rats produced diuresis, natriuresis and kaliuresis in the following 8 h daylight period. During the overnight cycle, consummatory behavior and excretion of sodium and potassium were reduced. Similar responses were obtained after IVT administration of cerebellar cortex (CB) or large amounts of plasma. SFO, CB and cerebral cortex (CC) were incubated in potassium-enriched CSF to enhance release of secretory products. Urine volume was increased 8 h after IVT injection of SFO media; in the overnight cycle, food consumption, absolute urinary sodium and potassium, and [Na+-a1 were reduced. These effects were not produced by IVT injection of CC or CB media, or equal amounts of plasma proteins. Additional experiments demonstrated that choroid plexi and SFO effects were similar and that the active SFO material was dialyzable and thermal stable. These data suggest that SFO contains a water-soluble substance which is released into a posassium-enriched medium. The material is heat stable, has a relatively low molecular weight, and alters salt-water balance after injection into ventricular cerebrospinal fluid.     

Impaired microvascular vasoconstrictive responses to vasopressin in septic rats

We have previously demonstrated that chronic alcohol consumption (8 to 10 weeks with ethanol as 36% of the caloric intake) does not exacerbate the effects of ischemia reperfusion injury on the heart. In those same studies, however, Gram-negative sepsis caused myocardial depression in both control and alcoholic rats, but also protected hearts from further damage due to ischemia-reperfusion. In the present study, we determined if preconditioning, a very short ischemia-reperfusion episode that protects the heart from more prolonged ischemia, would have similar effects on hearts from alcoholic and control rats with or without sepsis. Thus, rats were fed a liquid diet supplemented with ethanol or dextrin for 8 to 10 weeks. Some alcoholic and control rats were made septic with Escherichia coli injected into the subcutaneous space, whereas others received an injection of sterile saline. Isolated, isovolumically beating hearts were studied the following day. Hearts were made ischemic for 5 min, reperfused for 5 min, and then made ischemic for 35 min and reperfused for 25 min. Data from similar groups of hearts receiving only 35 min ischemia, and studied at the same time as the present groups, have been previously reported. The 5-min preconditioning episode was more effective in protecting hearts in the alcohol group than in the control group. Postischemic left ventricular developed pressure and +dP/dtmax were not significantly decreased from the preischemic values in the alcohol group, but were significantly decreased in the control group. The time to recovery of spontaneous contractions was decreased by preconditioning in the alcohol group but not in the control group, and the recovery of coronary flow was enhanced in the alcohol group, but not in the control group by pre-conditioning. Thus a single 5-min ischemic procedure was effective in protecting the heart from prolonged ischemia in the alcohol group, whereas it was not sufficient to elicit protection in the control group. Sepsis depressed preischemic function in both groups, but recovery from ischemia was complete.     

Bilateral cerebellar lesions disrupt conditioned eyelid responses in unrestrained rats.

Electromyographic eyelid responses in unrestrained rats were classically conditioned in a Pavlovian delay paradigm by using a tone conditioned stimulus (CS) and periorbital shock unconditioned stimulus (US). After eyelid conditioning was complete, bilateral electrolytic lesions were made in the dentate-interpositus region of the cerebellar nuclei. Initial eyelid conditioning was reliable and very similar to that previously observed in the rabbit, although the asymptotic eyelid responses contained a short-latency startle response in addition to the usual conditioned and unconditioned responses (CR and UR). Substantial decrements in CRs were observed in 13 of the 14 rats with accurately placed lesions. In contrast, startle responses and URs were unaffected. Results replicate the effects of cerebellar lesions on eyelid CRs in the rabbit and suggest that the anatomical basis of eyelid conditioning in both species is similar. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired recognition memory in patients with lesions limited to the hippocampal formation.

A recent literature survey of results from a widely used recognition memory test raised questions about the extent to which recognition memory impairment ordinarily occurs in human amnesia and, in particular, whether recognition memory is impaired at all after damage limited to the hippocampal region (J. P. Aggleton & C. Shaw, 1996). Experiment 1 examined the performance of 6 amnesic patients on 11 to 25 different recognition memory tests. Three patients had bilateral lesions limited primarily to the hippocampus (G.D.) or the hippocampal formation (W.H. and L.M.), as determined by postmortem, neurohistological analysis (N. Rempel-Clower, S. M. Zola, L. R. Squire, & D. G. Amaral, 1996). All 6 patients exhibited unequivocally impaired recognition memory. In Experiment 2, the 3 patients still available for study were each markedly impaired on a test of object recognition similar to the kind used to test recognition memory in nonhuman primates. Recognition memory impairment is a robust feature of human amnesia, even when damage is limited primarily to the hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Alberta Impaired Drivers' Project: A countermeasure to cope with the drinking driver.

Adaptation of alcohol countermeasures to a Canadian situation is described. The rationale and explicit procedure employed are outlined. A preliminary evaluation of behavioral outcome is given as data. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Circadian rhythms and partial recovery of regulatory drinking in rats after lateral hypothalamic lesions.

Eight sighted male albino rats that had recovered spontaneous ingestive behavior after lesions of the lateral hypothalamus were challenged with acute injections of hypertonic NaCl administered at different times during the day-night cycle. Nine intact controls were also studied. Following these injections, drinking was observed only during the nighttime. After morning injections Ss frequently waited until nightfall before drinking, whereas Ss injected at night showed much shorter delays in the behavioral response; a similar nocturnal predominance of drinking was seen after food deprivation and in the ad-lib situation. Studies in 6 blind lesioned Ss suggest that these effects were due to an endogenous circadian rhythm. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired sexual response after lesions of the paraventricular nucleus of the hypothalamus in male rats

N-methyl-D-aspartic acid (NMDA) or radiofrequency (RF) lesions were made in the paraventricular nucleus of the hypothalamus (PVH) of male rats. The rats were tested for copulation, noncontact erection (NCE) evoked by remote cues from estrous females, and (after RF lesions) reflexive erection. NMDA, which destroyed parvocellular but spared magnocellular neurons, caused no deficits in copulation but caused longer NCE latencies and fewer NCEs. Rats with RF lesions had parvo- and magnocellular neuron damage; these males copulated to ejaculation, but they had lower intromission ratios and longer ejaculatory latencies. RF-lesioned rats also had longer NCE latencies, and a smaller proportion of males displayed reflexive erection. Results indicate that the PVH participates in mediating erectile function in copula and ex copula, and that the parvo- and magnocellular PVH neurons may have different roles in mediating erection.     

Fragmented behavior sequences in rats with lateral hypothalamic lesions: An alternative reason for intrameal prandial drinking.

50 Sprague-Dawley and Long-Evans rats in Stages 3 or 4 after lateral hypothalamic lesions were studied in several feeding situations. As expected, Ss showed intrameal prandial drinking when dry food and water were available. Meals of liquid diet were interrupted by short bouts of activity, and saccharin drinking in Stage 3 was composed of many small drafts. It is suggested that these animals have a propensity to interrupt ongoing behaviors (fragmentation), which can account for general activity and wheel running that occurs along with intrameal prandial drinking. The probability of drinking during meals was decreased with water infusions and increased with NaCl infusion. When they were hungry, recovered laterals ate 4.5 g of dry food without pausing to drink. These new data raise questions concerning the state of the salivary-insufficiency (dry mouth) explanation of intrameal drinking; the fragmentation hypothesis can incorporate the data, and the possible neural correlates of this fragmentation are discussed. (49 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization of ionic currents of cells of the subfornical organ that project to the supraoptic nuclei

The subfornical organ (SFO) is a forebrain structure that converts peripheral blood-borne signals reflecting the hydrational state of the body to neural signals and then through efferent fibers conveys this information to several central nervous system structures. One of the forebrain areas receiving input from the SFO is the supraoptic nucleus (SON), a source of vasopressin synthesis and control of release from the posterior pituitary. Little is known of the transduction and transmission processes by which this conversion of systemic information to brain input occurs. As a step in elucidating these mechanisms, the present study characterized the ionic currents of dissociated cells of the SFO that were identified as neurons that send efferents to the SON. A retrograde tracer was injected into the SON area in eleven-day-old rats. After three days for retrograde transport of the label, the SFOs of these animals were dissociated and plated for tissue culture. The retrograde tracer was used to identify the soma of SFO cells projecting to the SON so that voltage-dependent ionic currents using whole-cell voltage clamp methods could be studied. The three types of currents in labeled SFO neurons were characterized as a 1) rapid, transient inward current that can be blocked by tetrodotoxin (TTX) characteristic of a sodium current; 2) slow-onset sustained outward current that can be blocked by tetraethylammonium (TEA) characteristic of a delayed rectifier potassium current; and 3) remaining outward current that has a rapid-onset and transient characteristic of a potassium A-type current.     

Impaired processing of local geometric features during navigation in a water maze following hippocampal lesions in rats.

Hippocampal damage impairs navigation with respect to information provided by the shape of an arena. Recent evidence has suggested that normal rats use local geometric information, as opposed to a global geometric representation, to navigate to a correct corner. One implication of this pattern of results is that hippocampal lesions may impair processing of 1 or more of the local geometric features of an environment. The authors therefore investigated the effects of hippocampal cell loss in rats on navigation to a hidden goal with respect to a variety of local cues in an environment with a distinctive shape. Rats with lesions of the hippocampus were impaired in discriminating a right-angled corner from its mirror image. However, they were able to use cues provided by an acute-angled corner (Experiment 1) or a local polarizing cue (Experiment 2). In contrast, lesioned rats were impaired in discriminating long versus short walls (Experiment 3). Results indicate that the hippocampus plays a role in disambiguating locations by processing (metric) information related to the distance between corners. (PsycINFO Database Record (c) 2010 APA, all rights reserved)