The effects of sodium appetite on the responses of cells in the zona incerta to the sight or ingestion of food, salt and water in sheep

Single-unit recordings were made from neurones in the zona incerta (ZI) of conscious sheep in response to the sight/visual approach or ingestion of various foods, salts and water. Animals were given parotid fistulae so that effects of sodium appetite, induced by not replacing the sodium lost in the saliva, could be assessed. When sodium depletion was prevented by giving the animals 1% sodium bicarbonate in their drinking water, the majority of cells (45 out of 49) responded most strongly to the sight or visual approach of food compared to water or salt. Four cells responded best to the sight of water, but none to the sight of salt and salt solutions. When a sodium appetite was stimulated, by removing the 1% sodium bicarbonate replacement for 4-6 days, there was a significant change in response profiles of ZI cells. The majority of cells responded most strongly to the sight of salts or salt solutions (35 out of 49) and significantly fewer cells responded most strongly to food (8 out of 49). The number of cells responding primarily to water was not affected (6 out of 49). For 3 cells responding to salts it was shown that, after repeated ingestion of salt over several hours, food became a more potent stimulus. A similar decreased response to foods during sodium depletion, and an increased one to salts, was seen in ZI cells which responded to the ingestion of both solids and liquids. These results show that changing an animal's motivational state produces significant changes in the responses of cells in the ZI responding to the sight or visual approach of substances.(ABSTRACT TRUNCATED AT 250 WORDS)     

The activity of neurones in the lateral hypothalamus and zona incerta of the sheep responding to the sight or approach of food is modified by learning and satiety and reflects food preference

Single unit recordings were made from neurones in the lateral hypothalamus and zona incerta of conscious sheep during the static visual presentation of food or visible approach of food towards the animal's mouth. The ability of this population of neurones to modulate their activity as a result of learning and satiety was investigated together with the extent to which their responsiveness reflected individual food preference. These neurones did not respond to either the sight or visible approach of a nonsense object or a food which they would not eat. Further, when the sight or approach of food which the animal desired to eat was not paired with ingestion the neurones rapidly extinguished their response. The magnitude of the neuronal response and the number of trials to extinction was dependent upon the animal's preference for a particular food: the most preferred food evoking the greatest response and being the most resistant to extinction. Following extinction the neuronal response to the sight or approach of food could be re-established after one or two trials with food reinforcement. If the sheep was repeatedly given the same food to eat the magnitude of the neuronal response and the number of trials to extinction gradually declined until no response occured when the animal refused to eat. These cells could also be induced to respond differentially to the approach of non-food objects dependent upon whether they were associated with a food reward or not. Thus a response could be evoked to the sight or approach of a black bottle if it was associated with a food reward but not to a yellow bottle unassociated with feeding. Acquired neuronal responses to novel foods could also be demonstrated.     

Role of the alpha 1- and alpha 2-adrenoceptors of the lateral hypothalamus in the dipsogenic response to central angiotensin II in rats.

The present experiments were conducted to investigate the role of the alpha 1- and alpha 2-adrenergic receptors of the lateral hypothalamus (LH) on the drinking response elicited by intracerebroventricular (i.c.v.) injections of carbachol and angiotensin II (AII) in rats. Clonidine (an alpha 2-adrenergic agonist) injected into the LH produced a dose-dependent reduction of the drinking responses elicited by i.c.v. administration of carbachol and AII. The alpha 1-adrenergic agonist phenylephrine injected into the LH reduced the dipsogenic response to i.c.v. AII, but not to carbachol. Injection of yohimbine (an alpha 2-adrenergic antagonist) and prazosin (an alpha 1-adrenergic antagonist) into the LH also reduced the water intake produced by i.c.v. injection of AII. Previous injection of alpha 1- or alpha 2-adrenergic antagonists into the LH increased the antidipsogenic effect of clonidine or phenylephrine injected into the same area on the water intake induced by i.c.v. AII. These results show that the alpha 1- and alpha 2-adrenergic receptors of the LH are involved in the control of drinking responses elicited by i.c.v. injection of AII in rats. They also show that clonidine, but not phenylephrine, suppresses the drinking induced by i.c.v. carbachol. The data suggest that the discharge of central alpha-adrenergic receptors has a dual (inhibitory and excitatory) effect on water intake induced by central AII.     

Modulation during learning of the responses of neurons in the lateral hypothalamus to the sight of food

Recordings were made from single neurons in the lateral hypothalamus and substantia innominata of the rhesus and squirrel monkey during feeding. A population of these neurons which altered their firing rates while the monkeys looked at food but not at nonfood objects was investigated. Because the responses of these neurons must have been affected by the previous experience of the animals, the activity of the neurons was measured during tasks in which the monkeys learned whether or not objects which they saw were associated with food. During visual discrimination tests these neurons came to respond when the monkey saw one stimulus associated with food (e.g., a black syringe from which the animal was fed glucose), but not when the monkey saw a different stimulus which was not associated with food (e.g., a white syringe from which the animal was offered saline). During extinction tests these units ceased to respond when the monkey saw a visual stimulus such as a peanut if the peanut was repeatedly not given to the monkey to eat. The learning or extinction behavior approximately paralleled the response of the neurons.The findings that the neurons in the lateral hypothalamus and substantia innominata respond when a monkey is shown food only if he is hungry, and as shown here, if as a result of learning the visual stimulus signifies food, provide information on a part of the brain which may be involved in feeding. The findings are consistent with other data which suggest that the responses of these neurons are involved in the autonomic and/or behavioral reactions of the animal to the sight of food.     

Effects of hunger on the responses of neurons in the lateral hypothalamus to the sight and taste of food

Recordings were made from single neurons in the monkey lateral hypothalamus and substantia innominata which had previously been shown to respond with an increase or decrease of their firing rates when the hungry monkey tasted food, and/or when he looked at food. It was found that the responsiveness of these neurons to food decreased over the course of a meal of glucose as satiety increased. When satiety, measured by whether the monkey rejected the glucose, was complete, there was no response of the neurons to the taste and/or to the sight of glucose. The spontaneous firing rates of these cells were not affected by the transitions from hunger to satiety. This modulation of responsiveness to food of hypothalamic cells was specific to them in that it was not seen in cells in the globus pallidus which responded in relation to swallowing and mouth movements, or in cells in the visual inferotemporal cortex which responded when the monkey looked at the glucose-containing syringe. On the basis of this and other evidence it is suggested that the hypothalamic cells described here could be involved in the autonomic, the endocrine, and/or the feeding responses which occur when an animal sees or tastes food.     

Role of theα1-andα2-adrenoceptors of the lateral hypothalamus in the dipsogenic response to central angiotensin II in rats

The present experiments were conducted to investigate the role of theα₁-andα₂-adrenergic receptors of the lateral hypothalamus (LH) on the drinking response elicited by intracerebroventricular (i.c.v) injections of carbachol and angiotensin II (AII) in rats. Clonidine (anα₂-adrenergic agonist) injected into the LH produced a dose-dependent reduction of the drinking responses elicited by i.c.v. administration of carbachol and AII. Theα₁-adrenergic agonist phenylephrine injected into the LH reduced the dipsogenic response to i.c.v. AII, but not to carbachol. Injection of yohimbine (anα₂-adrenergic antagonist) and prazosin (anα₁-adrenergic antagonist) into the LH also reduced the water intake produced by i.c.v. injection of AII. Previous injection ofα₁-orα₂-adrenergic antagonists into the LH increased the antidipsogenic effect of clonidine or phenylephrine injected into the same area on the water intake induced by i.c.v. AII. These results show that theα₁-andα₂-adrenergic receptors of the LH are involved in the control of drinking responses elicited by i.c.v. injection of AII in rats. They also show that clonidine, but not phenylephrine, suppresses the drinking induced by i.c.v. carbachol. The data suggest that the discharge of central α-adrenergic receptors has a dual (inhibitory and excitatory) effect on water intake induced by central AII.     

Clonidine and phenylephrine injected into the lateral hypothalamus inhibits water intake in rats

It has been demonstrated that peripheral or intracerebroventricular (i.c.v.) administration of the alpha 2-adrenoceptor agonist, clonidine, blocks the water intake induced by several dipsogenic stimuli in rats. In the present investigation we studied the effect of the injection of clonidine, phenylephrine, prazosin or yohimbine into the lateral hypothalamic area (LHA) on the water intake induced by water deprivation or central angiotensin II (AII) in rats. Rats with chronic cannulas implanted into the lateral ventricle and LHA were used. Injection of clonidine or phenylephrine into the LHA reduced the water intake produced by both water deprivation and i.c.v. injection of AII. Previous injection of the alpha 1- or alpha 2-adrenoceptor antagonists, prazosin or yohimbine, into the LHA reduced the antidipsogenic effect of clonidine or phenylephrine injected into the same area. These results suggest that the alpha 1- and alpha 2-adrenergic receptors of the hypothalamus are part of the central inhibitory system for the thirst produced by dehydration or central AII.     

Effects of lidocaine injections into the lateral parabrachial nucleus on dipsogenic and pressor responses to central angiotensin II in rats

This study investigated the effects of bilateral injections of the local anesthetic, lidocaine, into the lateral parabrachial nucleus (LPBN) on the dipsogenic and pressor responses induced by intracerebroventricular (i.c.v.) injection of angiotensin II (ANG II). Centrally injected ANG II (50 ng/1 μl) induced water intake (10.2 ± 0.8 ml/h) and pressor responses (22 ± 1mmHg). Prior bilateral injection of 10% lidocaine (200 nl) into the LPBN increased the water intake (14.2 ± 1.4 ml/h), but did not change the pressor response (17 ± 1 mmHg) to i.c.v. ANG II. Lidocaine alone injected into the LPBN also induced a pressor response (23 ± 3 mmHg). These results showing that bilateral LPBN injection of lidocaine increase water intake induced by i.c.v. ANG II are consistent with electrolytic and neurotoxic lesion studies and suggest that the LPBN is associated with inhibitory mechanisms controlling water intake induced by ANG II. These results also provides evidence that it is feasible to reversibly anesthetize this brain area to facilitate fluid-related ingestive behavior.     

Integration of visual and auditory information by superior temporal sulcus neurons responsive to the sight of actions

Processing of complex visual stimuli comprising facial movements, hand actions, and body movements is known to occur in the superior temporal sulcus (STS) of humans and nonhuman primates. The STS is also thought to play a role in the integration of multimodal sensory input. We investigated whether STS neurons coding the sight of actions also integrated the sound of those actions. For 23% of neurons responsive to the sight of an action, the sound of that action significantly modulated the visual response. The sound of the action increased or decreased the visually evoked response for an equal number of neurons. In the neurons whose visual response was increased by the addition of sound (but not those neurons whose responses were decreased), the audiovisual integration was dependent upon the sound of the action matching the sight of the action. These results suggest that neurons in the STS form multisensory representations of observed actions.     

Convergence of signals in the zona incerta for angiotensin-mediated and osmotic thirst

Extracellular single-unit activity was recorded from 109 neurons in the diencephalon of urethane-anesthetized rats. Injections of angiotensin II (ANG II) into the subfornical organ (SFO) increased the activity of 15 zona incerta (ZI) neurons and decreased the activity of 9. Injections of ANG II into the SFO increased the activity of 8 lateral hypothalamic neurons and decreased the activity of 7. Of the units which responded to the injection of ANG II into the SFO, 9 neurons in the ZI and 5 in the lateral hypothalamus (LH) also responded to injections of hyperosmotic saline into the medial preoptic area. The SFO and preoptic area are possible sites of receptors for ANG II-mediated and osmotic thirst, respectively, and the present results suggest that signals important for the initiation of these thirst mechanisms converge on neurons in the ZI and LH. These findings are discussed in relation to other neural structures that have been implicated in the regulation of water intake.     

Evidence for a role of endogenous nesfatin-1 in the control of water drinking

Nesfatin-1, a post-translational product of the nucleobindin-2 (NucB2) gene, is produced in several brain areas known to be important in neuroendocrine, autonomic and metabolic function, including the hypothalamus and medulla. The hallmark action of the peptide is its ability at picomole doses to inhibit food and water intake in rodents and, indeed, the effect on water intake is more pronounced than that on food intake. In preliminary studies, we observed a decrease in hypothalamic NucB2 expression in response to overnight water deprivation even when food was present, which reversed when water was returned to the animals. We therefore hypothesised that the effect of nesfatin-1 on water drinking was independent of its anorexigenic action. Indeed, rats administered nesfatin-1 i.c.v. consumed significantly less water than controls in response to a subsequent, dipsogenic dose of angiotensin II, or upon return of water bottles after 18 h of fluid restriction (food present), or in response to a hypertonic challenge. Pretreatment with an antisense oligonucleotide against nesfatin-1 significantly reduced levels of immunoreactive nesfatin-1 in the hypothalamic paraventricular nucleus and resulted in exaggerated drinking responses to angiotensin II. The results obtained in the present study suggest that locally produced nesfatin-1 may be an important component of the hypothalamic mechanisms controlling fluid and electrolyte homeostasis.     

Cardiovascular and dipsogenic effects of angiotensin II administered i.c.v. in Long-Evans and Brattleboro rats

The concurrent cardiovascular and dipsogenic effects produced by i.c.v. administration of angiotensin II (AII) have been investigated in vasopressin-deficient (Brattleboro) and control (Long-Evans) rats. When animals were allowed to drink during testing, the pressor effect of i.c.v. AII (500 ng) in Long-Evans rats (26 +/- 3/26 +/- 3 mm Hg) was significantly greater than that produced when drinking water was not available (19 +/- 2/18 +/- 2 mm Hg). There was a significant decrease in heart rate only when water was available. There was no pressor response to i.c.v. AII in Brattleboro rats not allowed to drink, whereas blood pressure increased by 17 +/- 3/14 +/- 1 mm Hg in response to i.c.v. AII when drinking water was present. There were no significant changes in heart rate following i.c.v. AII in Brattleboro rats. When baseline drinking was taken into account, Brattleboro rats still drank significantly more water than Long-Evans rats in response to i.c.v. AII. Pretreatment of Long-Evans rats with the V1 vasopressin antagonist, D(CH2)5Tyr(Et)DAVP, decreased the pressor effect of i.c.v. AII to a level not significantly different from that of Brattleboro rats allowed to drink. Under these conditions the amount drunk by Long-Evans rats was not significantly less than that drunk by Brattleboro rats. These results confirm that the central pressor actions of AII are mediated, in part, by release of vasopressin and suggest that the greater dipsogenic effect of i.c.v. AII in Brattleboro compared with Long-Evans rats may be due, partly, to its lesser pressor activity in these animals.     

Occlusion of rostroventral 3rd ventricle abolishes drinking but not AVP release in response to central osmotic stimulation

Dogs were implanted with a device for chronic cannulation of the anterior part of the 3rd ventricle (A3V). Intracerebroventricular (i.c.v.) infusion of artificial cerebrospinal fluid (CSF) containing 0.35 M NaCl into the A3V of 7 normally hydrated dogs induced thirst (average water intake 11.8 +/- 2.0 ml.kg-1 b. wt.) and significantly increased arginine-vasopressin (AVP) concentration in the blood plasma from 3.4 +/- 0.3 to 8.2 +/- 1.2 pg.ml-1. When repeating the i.c.v. hypertonic infusion at intervals of one week or more in two dogs, its dipsogenic effect vanished within 3-5 months. X-ray analysis revealed an occlusion of the rostroventral part of the A3V. Subsequent controls on 3 other dogs confirmed that the dipsogenic response to i.c.v. osmotic stimulation was abolished in association with similar partial occlusions of the A3V. However, this stimulus still produced a significant increase of plasma AVP from 3.7 +/- 0.5 to 5.7 +/- 0.7 pg.ml-1 in the 5 dogs. Control of drinking in these dogs was otherwise unimpaired as indicated by their normal plasma osmolalities. Histological examination revealed that the loss of the dipsogenic response to i.c.v. infusion of 0.35 M NaCl was in each case associated with fibrinous occlusion of the A3V between its rostral wall and the mass intermedia, preventing the passage of the infusate to the supraoptic and infundibular recesses.     

Neurons in the posterior insular cortex are responsive to gustatory stimulation of the pharyngolarynx, baroreceptor and chemoreceptor stimulation, and tail pinch in rats

Extracellular unit responses to gustatory stimulation of the pharyngolaryngeal region, baroreceptor and chemoreceptor stimulation, and tail pinch were recorded from the insular cortex of anesthetized and paralyzed rats. Of the 32 neurons identified, 28 responded to at least one of the nine stimuli used in the present study. Of the 32 neurons, 11 showed an excitatory response to tail pinch, 13 showed an inhibitory response, and the remaining eight had no response. Of the 32 neurons, eight responded to baroreceptor stimulation by an intravenous (i.v.) injection of methoxamine hydrochloride (Mex), four were excitatory and four were inhibitory. Thirteen neurons were excited and six neurons were inhibited by an arterial chemoreceptor stimulation by an i.v. injection of sodium cyanide (NaCN). Twenty-two neurons were responsive to at least one of the gustatory stimuli (deionized water, 1.0 M NaCl, 30 mM HCl, 30 mM quinine HCl, and 1.0 M sucrose); five to 11 excitatory neurons and three to seven inhibitory neurons for each stimulus. A large number of the neurons (25/32) received converging inputs from more than one stimulus among the nine stimuli used in the present study. Most neurons (23/32) received converging inputs from different modalities (gustatory, visceral, and tail pinch). The neurons responded were located in the insular cortex between 2.0 mm anterior and 0.2 mm posterior to the anterior edge of the joining of the anterior commissure (AC); the mean location was 1.2 mm (n=28) anterior to the AC. This indicates that most of the neurons identified in the present study seem to be located in the region posterior to the taste area and anterior to the visceral area in the insular cortex. These results indicate that the insular cortex neurons distributing between the taste area and the visceral area receive convergent inputs from gustatory, baroreceptor, chemoreceptor, and nociceptive organs.     

The Hypothalamic Peptides, β-Endorphin, Neuropeptide K and Interleukin-1β, and the Opiate Morphine, Enhance the Excitatory Amino Acid-Induced LH Release under the Influence of Gonadal Steroids

Several hypothalamic neuropeptides and amino acids are known to inhibit or excite pituitary luteinizing hormone (LH) release, but the precise interplay between these 2 classes of signals in episodic LH discharge is not known. In this study, we have evaluated the interaction between neuropeptides shown previously to inhibit LH release in castrated rats and the excitatory amino acid agonist, N-methyl-D-aspartate (NMDA), on LH release in intact male rats. Rats received a permanent intracerebroventricular (i.c.v.) cannula and 9–12 days later an intrajugular cannula for frequent blood sampling. The next day, rats received i.c.v. either saline (SAL, 3 μl, controls) or a neuropeptide: the opioid β-endorphin (β-END; 2.9 nmol), the tachykinin neuropeptide K (NPK, 2.5 nmol) or the cytokine interleukin-1β (IL-1β, 5.9 pmol) in SAL. The LH response to 2 consecutive i.v. injections of NMDA (5 mg/kg) at 30 min intervals was evaluated. In control rats, each NMDA injection evoked a significant release of LH at 10 min. Quite unexpectedly, the three peptides, instead of exerting an inhibitory effect, enhanced the LH response to NMDA. The peak plasma LH levels after each NMDA injection and the cumulative LH responses were significantly higher in peptide-treated than in control rats. This peculiar ability of the peptides that inhibit LH release in castrated rats, to potentiate the NMDA-induced LH release in the presence of gonadal steroids was further validated in female rats treated with an opiate receptor agonist, morphine (MOR) which is also known to suppress LH release in ovariectomized rats. Rats were ovariectomized (ovx) and 14 days later received one estradiol-17β-containing Silastic® capsule s.c. (E₂, 300 μg/ml oil). In addition, each rat received 1 pellet of placebo (PLA, control) or MOR (75 mg/pellet) s.c. followed 2 days later by 2 additional PLA or MOR pellets, and an intrajugular cannula. The LH response of these rats to 2 i.v. injections of NMDA (5 mg/kg) 30 min apart was evaluated. The results showed that each injection of NMDA elicited a pulse of LH with peak levels at 10 min in control rats. However, in MOR-treated rats the LH response to NMDA was amplified; peak and cumulative LH responses were significantly higher in these rats. To ascertain whether this augmentation of LH response induced by MOR was exerted at the hypothalamic level, the effects of NMDA on in vitro LHRH release from the median eminence-arcuate nucleus (ME-ARC) fragment of ovx rats similarly pretreated with E₂ and PLA or MOR were compared. The results showed that LHRH efflux in response to 50 mM NMDA alone and in combination with 23 mM KCl was higher in MOR-treated than in control rats. Cumulatively, these results show that activation of hypothalamic opioid, tachykinin and cytokine receptors which ordinarily result in suppression of LH release in gonadal steroid deficient rats, concurrently enhances the excitatory LH response of NMDA under the influence of gonadal steroids. These unexpected findings reveal a novel modality of involvement of these peptides in the hypothalamic control of pituitary LH release. While these peptides may play a role in attenuating LH secretion in intact rats, our studies are in accord with the view that these peptides enhance the response of the hypothalamo-pituitary axis to incoming signals, including the excitatory amino acids, that excite the release of LH.     

Amygdaloid neuronal responses to complex visual stimuli in an operant feeding situation in the monkey

In chronically prepared monkeys, 337 neurons were recorded from the anterolateral amygdala during an operant task that required visual discrimination. Twelve percent (39/337) of the neurons responded to one or more of food or non-food visual stimuli. A subset of these responsive neurons was selectively sensitive to the sight of non-food objects with aversive associations. Simultaneous presentation of a food stimulus with the aversive object inhibited the response of these neurons. These response characteristics could not be explained by simple sensory processing of the visual stimuli. It is suggested that the amygdala plays an important role in the elaboration of motivational behavior by using the complex or associative properties of visual stimuli.     

Role of monkey hippocampus in recognition of food and nonfood

To investigate the role of the hippocampal formation (HF) in feeding behavior, single neuron activity in the monkey HF was recorded during performance of an operant task that included food/nonfood discrimination, drinking, and active avoidance. Of 837 neurons recorded in the HF, 155 responded to the sight of one or more objects. Of these, 82 responded to the sight of different objects with different response magnitudes, and some of these 82 responded predominantly to food-related (rewarding) objects or nonfood, aversive objects. The magnitude of response of neurons that responded predominantly to food was not necessarily correlated with the order of animal's preference for those kinds of food. For some neurons that responded predominantly to food or nonfood, effects of extinction or reversal learning on the neuronal responses were tested, and most of the neurons tested maintained their original responsiveness even after behavioral extinction or reversal learning was accomplished. The results suggest that these HF neurons may be involved in preservation of past information concerning food or nonfood.     

Tachyphylaxis of dipsogenic activity to intracerebroventricular administration of angiotensins

Repeated intracerebroventricular (i.c.v.) administration of angiotensin II (AII) and angiotensin III (AIII) induced dipsogenic tachyphylaxis in the Sprague-Dawley rat. AIII caused a rapid suppression of drinking, whereas AII showed a progressive decline of water consumption with repeated injections. Tachyphylaxis due to the repeated i.c.v. application of AII failed to abolish subsequent drinking induced by neurotensin or carbachol, suggesting that the tachyphylaxis may be specific to the angiotensinergic system. However, AII-induced tachyphylaxis caused a complete elimination of bestatin-induced drinking which was anticipated given the likelihood that this aminopeptidase B inhibitor has its dipsogenic effect by inhibiting degradation of endogenous angiotensins. Angiotensin-induced tachyphylaxis responses could not be attributed to diminished dipsogenic activity due to volemic expansion of either the cerebroventricular space or gastrointestinal tract. These results concerned with central tachyphylaxis are consistent with previous findings in the periphery and suggest that desensitization of angiotensin receptors occurs in both populations.     

Pituitary gland responsiveness to LHRH and LHRH neuronal responsiveness to excitatory stimuli are severely impaired in female rats treated neonatally with high doses of androgen

Treatment of neonatal female rats with androgen renders these animals permanently sterile as adults. Previously, we reported that these androgen-sterilized rats (ASR) do not respond to the positive feedback effects of estrogen by having LH surges. We also reported that this defect might be due to the failure of these animals to show increased hypothalamic norepinephrine turnovers (an index of secretion) in response to steroid treatment. Although LHRH-catecholamine synapses are established before or at birth, whether such synapses are functions remains to be resolved. Accordingly, the present studies, female rats were ggiven 1.25 mg of testosterone propionate at 5 days of age and, at 100 days of age, these ASR and controls were ovariectomized and treated with estradiol. In these animals, we examined whether activation of medullary A1 noradrenergic neurons would amplify LH release following preliminary depolarization of LHRH neurons with an electrochemical stimulus (ECS). As well, we reexamined whether LHRH neuronal responsiveness to exogenous NE and pituitary responsiveness to LHRH differ in controls versus ASR. In controls, two pulses of LHRH given 60 min apart elicited increases in plasma LH with the second pulse inducing greater LH release than the first pulse. In ASR, significantly less LH was released after either LHRH pulse and particularly after the second pulse. When the spacing between the two LHRH pulses was reduced to 25 min, equivalent levels of LH release occured in controls and ASR after the second pulse. The i.c.v. infusion of NE induced a rapid rise in plasma LH in both controls and ASR although the peak LH responses (at 10 min) were significantly less in the ASR group. When the medial preoptic area (MPOA) was ECS, plasma LH increased in both groups of rats but significantly less LHRH was released in ASR. Combined MPOA-ECS+i.c.v. NE in controls and ASR resulted in amplification of LH release above that obtained after only MPOA-ECS. However, the amount of LH released in ASR was significantly less than controls. In the final study, bilateral MPOA-ECS was performed and 20 min later the right A1 cell group was electrically stimulated (ES) for 15 min. In control rats, combined MPOA-ECS+A1-ES resulted in greater LH release than occured after MPOA-ECS alone. Although similar combined preoptic+A1 stimulation also amplified LH release in ASR, the plasma LH concentrations were significantly less than controls. From these studies we conclude that: (1) pituitary responsiveness to LHRH is less in ASR than controls; (2) LHRH neuronal responsiveness to various excitatory stimuli also is less in ASR compared to controls; (3) the responses of LHRH neurons to Ai-ES in controls and ASR indicate that endogenous NE signals evoke LHRH release.     

Neuropeptide Y and food intake in fasted rats: effect of naloxone and site of action

Central administration of neuropeptide Y (NPY) induces food intake in freely feeding animals and this effect is mediated by hypothalamic sites. Little is known, however, about the effect of NPY on food intake and site of action in food-deprived animals. To examine this further, 24-h fasted rats received injections of saline or NPY into the lateral cerebral ventricle (10 micrograms/10 microliters; n = 8) or into the lateral (LH) or ventromedial hypothalamus (VMH) (1 microgram/0.5 microliters; n = 44). In addition, intracerebroventricular (i.c.v.) injections of NPY were carried out with or without i.c.v. naloxone (25 micrograms), a specific opioid receptor antagonist. During the first 40 min food intake was not different with or without NPY. After 60 and 120 min, food intake was 5.9 +/- 0.4 g and 8.3 +/- 0.6 g with i.c.v. saline which was significantly augmented by i.c.v. NPY to 8.7 +/- 0.9 g and 14.4 +/- 1.5 g, respectively (P less than 0.05). This increase in food consumption was due to a prolongation of feeding time. The opioid receptor antagonist naloxone significantly augmented latency to feed, both in the absence and presence of NPY (8.0 vs 1.7 min or 14.7 vs 2.8 min, respectively) and abolished the NPY-induced increase in food intake. Following intrahypothalamic injection of NPY, an increase in food intake (greater than 20%) was observed in 50% of the histologically identified LH and VMH sites, but only in 15% of the injection sites outside the LH/VMH.(ABSTRACT TRUNCATED AT 250 WORDS)