Stimulation Of Posterior Hypothalamus Research Articles

EHMTI-0279. Deep brain stimulation for refractory chronic cluster headache

Chronic cluster headache (CCH) is an excruciating, unilateral headache with recurrent episodes of severe pain associated with ipsilateral autonomic features. 10-20% of patients are refractory to medical management. We present a prospective cohort of 19 patients with intractable CCH treated with posterior hypothalamic deep brain stimulation (DBS).

Posterior Hypothalamic Deep Brain Stimulation. The Impact on Cluster Headache Control and Other Indications

Posterior Hypothalamic Deep Brain Stimulation. The Impact on Cluster Headache Control and Other Indications

Secondary chronic cluster headache treated by posterior hypothalamic deep brain stimulation: First reported case

Deep brain stimulation (DBS) of the posterior hypothalamus (pHyp) has been reported as an effective treatment for primary, drug-refractory and chronic cluster headache (CCH). We here describe the use of such a procedure for the treatment of secondary CCH due to a neoplasm affecting the soft tissues of the right hemiface. A 27-year-old man affected by infiltrating angiomyolipoma of the right hemiface who subsequently developed drug refractory homolateral CCH underwent DBS of the right pHyp region at the Fondazione IRCCS Istituto Nazionale Neurologico Carlo Besta. After surgery, the patient presented a significant reduction in frequency of pain bouts. However, because of a subsequent infection, the entire system was removed. After re-implantation of the system, successful outcome was observed at 2 years follow-up. This brief report shows the feasibility of pHyp DBS in secondary drug-refractory CCH syndromes; future reports are needed in order to confirm our positive result.

Efficacy of hypothalamic stimulation for chronic drug-resistant cluster headache

The study of Seijo et al. recently published in this journal (1) provides further convincing evidence that posterior hypothalamic stimulation can be an effective treatment for carefully selected patients with drug-resistant chronic cluster headache. All five patients had a severe condition that had not responded to either drugs or previous surgical treatments. A number of aspects of the study deserve closer examination.

Switching on the deep brain stimulation: Effects on cardiovascular regulation and respiration

BackgroundObjective of this study was to evaluate the acute cardiovascular and respiratory effects of switching on the deep brain stimulation in the follow up of nine Parkinson's disease patients with subthalamic nucleus stimulation and six cluster headache patients with posterior hypothalamic area stimulation. MethodsSystolic and diastolic blood pressure, heart rate, and respiratory rate were monitored continuously during supine rest in both groups. Each patient was assessed in two conditions: resting supine with stimulator off and with stimulator on. ResultsIn supine resting condition switching on the DBS induced no significant changes (p>0.05) in systolic and diastolic blood pressure as well as in heart rate and respiratory rate, in both groups of patients, either taking 1min or 10 heartbeats as a sample for analysis. ConclusionsSwitching on the DBS does not modify heart rate, blood pressure nor respiratory rate in both Parkinson and cluster headache patients under resting conditions.

Posterior hypothalamic nucleus deep brain stimulation restores locomotion in rats with haloperidol-induced akinesia but not skilled forelimb use in pellet reaching and lever pressing

Recent studies have shown that electrical stimulation of the posterior hypothalamic nucleus (PH) facilitates locomotion in control rats, and rats were made akinetic by dopaminergic blockade via haloperidol or dopamine depletion by the neurotoxin 6-hydroxydopamine. These findings suggest that PH stimulation might be a promising treatment for akinesia associated with dopamine loss in Parkinson's disease. The present study further examined the positive effects of PH stimulation on behavior by characterizing its potential facilitatory effects on tasks that require skilled movements. Rats were trained to reach for food pellets with a forelimb (skilled reaching) or press a bar in an operant conditioning task for food. PH stimulation in undrugged rats not only facilitated locomotion in each of the tasks, but also impaired performance of the skilled movement components of the tasks. Haloperidol reduced locomotion and skilled movement, and PH stimulation only restored locomotion. The results are discussed in relation to the idea that PH stimulation selectively facilitates locomotor behavior and may have limited use in restoring impairments in skilled movements and consummatory behavior that results from dopaminergic depletion.

Failure of Verapamil and Diltiazem to Attenuate the Pressor Response to Hypothalamic Stimulation: A Possible Mechanism

The effects of verapamil or diltiazem on pressor responses to posterior hypothalamic stimulation, injected noradrenaline or tyramine were studied in urethane-anaesthetized normotensive, deoxycorticosterone acetate (DOCA), renal and spontaneously hypertensive rats at the early and established phases of hypertension. Pressor responses to the pressor stimuli were significantly enhanced in the early and established phases of hypertension when compared with the normotensives. While the magnitude of pressor responses in the established phase of renal or spontaneously hypertensive rats was significantly higher (P less than 0.05) than the corresponding value in the early phase, in contrast, the pressor response in the early phase of DOCA hypertension was significantly higher than that of the established phase. Verapamil or diltiazem significantly (P less than 0.005) inhibited pressor responses to injected noradrenaline or tyramine in all groups of rats but not that to hypothalamic stimulation, irrespective of the stage of hypertension. When the probable mechanism of the hypothalamic pressor response's resistance to the calcium antagonists was studied in-vitro, ATP significantly (P less than 0.005) inhibited the relaxant effect of the calcium antagonists in the rat aortic strips. Our data indicate that verapamil or diltiazem is ineffective in inhibiting the pressor response to posterior hypothalamic stimulation. The probable mechanism of the resistance and the clinical implication of the findings are discussed.

Functional MRI response and correlated electrophysiological changes during posterior hypothalamic nucleus deep brain stimulation

Identification of active networks involved in behavior is central to understanding brain function as an emergent property. Functional magnetic resonance imaging (fMRI) allows the identification of areas with increased or decreased activity, but the cellular correlates to changes in fMRI response is still controversial. Deep brain stimulation of the posterior hypothalamic nucleus (PH) is known to facilitate locomotor behaviors and rescue locomotion in rodent models of parkinsonian akinesia by an unknown mechanism. Here, we performed 9.4 T fMRI during deep brain stimulation of PH in the anesthetized rat as a model system to explore the network substrates for its behavioral consequences. In addition, multi-unit and field potential recordings were made to examine the physiological correlates to changes in fMRI response. The most robust and reliable MR signal increases were observed in the somatosensory and motor cortices, with minor limbic and sparse thalamic activation. Electrophysiological experiments demonstrated that increased fMRI response in the neocortex corresponds to general increases in spiking activity, decreased slow oscillations and increased delta band activity. Forelimb movements evoked by intracortical microstimulation had reduced thresholds and larger representational (motor map) areas during and following PH stimulation. These findings identify the sensorimotor cortices as major contributors for behavioral effects of PH stimulation, and that coincident increase in spiking, synaptic activity and MR signal reflect functional facilitation of neocortical output.

SUCCESSFUL TREATMENT OF CHRONIC PAROXYSMAL HEMICRANIA WITH POSTERIOR HYPOTHALAMIC STIMULATION

Chronic paroxysmal hemicrania (CPH) is a rare, unilateral primary headache syndrome. Recent studies suggest hypothalamic dysfunction as the likely cause of CPH. Therapeutic response to deep brain stimulation of the hypothalamus has been observed in the treatment of related trigeminal autonomic cephalgias. We explored the therapeutic effectiveness of posterior hypothalamic stimulation for the treatment of CPH in a patient intolerant of medical management. A 43-year-old woman with CPH reported acute onset of lancinating, unilateral headache pain focused about the right orbit. These debilitating headaches were accompanied by ipsilateral nasal congestion, conjunctival injection, tearing, and ptosis lasting minutes before resolving spontaneously. The patient exhausted attempts at medical management. A deep brain stimulator microelectrode was placed under stereotactic guidance. The posterior hypothalamic target was 3 mm posterior, 5 mm inferior, and 2 mm ipsilateral to the midcommissural point. The electrode was connected to a standard pulse generator and set to final amplitude of 1.5 V, a pulse width of 60 microseconds, and a frequency of 185 Hz. The patient's headache symptoms were durably alleviated with intraoperative activation. No complications were observed. This preliminary success suggests a role for posterior hypothalamic stimulation as a safe and effective treatment in patients with medically refractory CPH. As a therapeutic incremental innovation, this off-label use of technology for symptomatic therapy contributes to results of studies that support a central pathophysiological role for hypothalamic dysfunction in headaches classified among the trigeminal autonomic cephalgias.

Activation of the retrotrapezoid nucleus by posterior hypothalamic stimulation.

The retrotrapezoid nucleus (RTN) contains chemically defined neurons (ccRTN neurons) that provide a pH-regulated excitatory drive to the central respiratory pattern generator. Here we test whether ccRTN neurons respond to stimulation of the perifornical hypothalamus (PeF), a region that regulates breathing during sleep, stress and exercise. PeF stimulation with gabazine increased blood pressure, phrenic nerve discharge (PND) and the firing rate of ccRTN neurons in isoflurane-anaesthetized rats. Gabazine produced an approximately parallel upward shift of the steady-state relationship between ccRTN neuron firing rate and end-tidal CO(2), and a similar shift of the relationship between PND and end-tidal CO(2). The central respiratory modulation of ccRTN neurons persisted after gabazine without a change in pattern. Morphine administration typically abolished PND and reduced the discharge rate of most ccRTN neurons (by 25% on average). After morphine administration, PeF stimulation activated the ccRTN neurons normally but PND activation and the central respiratory modulation of the ccRTN neurons were severely attenuated. In the same rat preparation, most (58%) ccRTN neurons expressed c-Fos after exposure to hypercapnic hyperoxia (6-7% end-tidal CO(2); 3.5 h; no hypothalamic stimulation) and 62% expressed c-Fos under hypocapnia (approximately 3% end-tidal CO(2)) after PeF stimulation. Under baseline conditions (approximately 3% end-tidal CO(2), hyperoxia, no PeF stimulation) few (11%) ccRTN neurons expressed c-Fos. In summary, most ccRTN neurons are excited by posterior hypothalamic stimulation while retaining their normal response to CNS acidification. ccRTN neurons probably contribute both to the chemical drive of breathing and to the feed-forward control of breathing associated with emotions and or locomotion.

Lessons From 8 Years' Experience of Hypothalamic Stimulation in Cluster Headache

Neuroimaging studies in cluster headache (CH) patients have increased understanding of attack-associated events and provided clues to the pathophysiology of the condition. They have also suggested stimulation of the ipsilateral posterior inferior hypothalamus as a treatment for chronic intractable CH. After 8 years of experience, stimulation has proved successful in controlling the pain attacks in almost 60% of chronic CH patients implanted at various centres. Although hypothalamic implant is not without risks, it has generally been performed safely. Implantation affords an opportunity to perform microrecordings of individual posterior hypothalamic neurons. These studies are at an early stage, but suggest the possibility of identifying precisely the target site by its electrophysiological characteristics. Autonomic studies of patients undergoing posterior hypothalamic stimulation provide further evidence that long-term stimulation is safe, revealing that it can cause altered modulation of the mechanisms of orthostatic adaptation without affecting the baroreflex, cardiorespiratory interactions or efferent sympathetic and vagal functions. Chronically stimulated patients have an increased threshold for cold pain at the site of the first trigeminal branch ipsilateral to the stimulated side; when the stimulator is switched off, changes in sensory and pain thresholds do not occur immediately, suggesting that long-term stimulation is required to induce sensory and nociceptive changes. Posterior inferior hypothalamic stimulation is now established as a treatment for many chronic CH patients. The technique is shedding further light on the pathophysiology of the disease, and is also providing clues to functioning of the hypothalamus itself.

Deep brain stimulation in headache

The therapeutic use of deep brain stimulation to relieve intractable pain began in the 1950s. In some patients, stimulation of the periaqueductal grey matter induced headache with migrainous features, indicating a pathophysiological link between neuromodulation of certain brain structures and headache. Neuroimaging studies have revealed specific activation patterns in various primary headaches. In the trigeminal autonomic cephalgias, neuroimaging findings support the hypothesis that activation of posterior hypothalamic neurons have a pivotal role in the pathophysiology and prompted the idea that hypothalamic stimulation might inhibit this activation to improve or eliminate the pain in intractable chronic cluster headache and other trigeminal autonomic cephalgias. Over the past 6 years, hypothalamic implants have been used in various centres in patients with intractable chronic cluster headache. The results are encouraging: most patients achieved stable and notable pain reduction and many became pain free. All deep-brain-electrode implantation procedures carry a small risk of mortality due to intracerebral haemorrhage. Before implantation, all patients must undergo complete preoperative neuroimaging to exclude disorders associated with increased haemorrhagic risk. No substantial changes in hypothalamus-controlled functions have been reported during hypothalamic stimulation. Hypothalamic stimulation may also be beneficial in patients with SUNCT (short-lasting, unilateral, neuralgiform headache attacks with conjunctival injection and tearing)--a disorder with close clinical and neuroimaging similarities to the cluster headache. WHERE NEXT?: Neuroimaging findings in patients undergoing posterior hypothalamic stimulation have shown activation of the trigeminal nucleus and ganglion. This evidence supports the hypothesis that hypothalamic stimulation exerts its effect by modulating the activity of the trigeminal nucleus caudalis, which in turn might control the brainstem trigeminofacial reflex--thought to cause cluster headache pain. Future studies might determine whether other areas of the pain matrix are suitable targets for neuromodulation in patients with cluster headache who do not respond to hypothalamic modulation.

CLUSTER HEADACHE

Objective: To describe the results of deep brain stimulation of the ipsilateral posterior hypothalamus for the treatment of drug‐resistant chronic cluster headaches (CHs). A technique for electrode placement is reported. Methods: Because recent functional studies suggested hypothalamic dysfunction as the cause of CH bouts, we explored the therapeutic effectiveness of posterior hypothalamic stimulation for the treatment of CHs. Five patients with intractable chronic CHs were treated with long‐term, high‐frequency, electrical stimulation of the posterior hypothalamus. Electrodes were stereotactically implanted in the following position: 3 mm behind the midcommissural point, 5 mm below the midcommissural point, and 2 mm lateral to the midline. Results: Since this treatment, all five patients continue to be pain‐free after 2 to 22 months of follow‐up monitoring. Two of the five patients have remained pain‐free without any medication, whereas three of the five required low doses of methysergide (two patients) or verapamil (one patient). No adverse side effects of chronic, high‐frequency, hypothalamic stimulation have been observed, and we have not encountered any acute complications resulting from the implant procedure. There have been no tolerance phenomena. Conclusion: These preliminary results indicate a role for posterior hypothalamic stimulation, which was demonstrated to be safe and effective, in the treatment of drug‐resistant chronic CHs. These data point to a central pathogenesis for chronic CHs. Comment.—This study is the big kahuna, the description of the surgical treatment of cluster headache by implantation of a radiostimulator in the “hypothalamic cluster generator” first described by Dr. Peter Goadsby's group (May A, Bahra A, Buchel C, Frackowiak RS, Goadsby PJ. PET and MRA findings in cluster headache and MRA in experimental pain. Neurology. 2000; 55:1328‐1335). This is an exquisite match of pathophysiologic understanding and clinical intervention. The patients operated upon by Dr. Franzini's group were severely impaired with refractory cluster headache. Additional patients have received the procedure in Belgium, and I anxiously await published results. The standard surgical procedure for these patients in the United States has been radiofrequency trigeminogangliorhizolysis, described in great detail by Dr. Ninan Mathew in an abstract (Mathew NT, Hurt W, Kailasam J, Meadors L. Percutaneous radiofrequency trigeminal rhizolysis in intractable chronic cluster headache: 20 years experience, 125 patients [abstract]. Neurology. 2002; 58(suppl 3):A495‐A496). Probably, depending on whether the Belgian physicians reproduce the Italian results, the next step will be to try this procedure in North America, because it may offer greater specificity and higher success rates for our most refractory and desperate patients with cluster headache. SJT

Stimulation of the Posterior Hypothalamus for Treatment of Chronic Intractable Cluster Headaches: First Reported Series

Abstract OBJECTIVE To describe the results of deep brain stimulation of the ipsilateral posterior hypothalamus for the treatment of drug-resistant chronic cluster headaches (CHs). A technique for electrode placement is reported. METHODS Because recent functional studies suggested hypothalamic dysfunction as the cause of CH bouts, we explored the therapeutic effectiveness of posterior hypothalamic stimulation for the treatment of CHs. Five patients with intractable chronic CHs were treated with long-term, high-frequency, electrical stimulation of the posterior hypothalamus. Electrodes were stereotactically implanted in the following position: 3 mm behind the midcommissural point, 5 mm below the midcommissural point, and 2 mm lateral to the midline. RESULTS Since this treatment, all five patients continue to be pain-free after 2 to 22 months of follow-up monitoring. Two of the five patients have remained pain-free without any medication, whereas three of the five required low doses of methysergide (two patients) or verapamil (one patient). No adverse side effects of chronic, high-frequency, hypothalamic stimulation have been observed, and we have not encountered any acute complications resulting from the implant procedure. There have been no tolerance phenomena. CONCLUSION These preliminary results indicate a role for posterior hypothalamic stimulation, which was demonstrated to be safe and effective, in the treatment of drug-resistant chronic CHs. These data point to a central pathogenesis for chronic CHs.

Stimulation of the Posterior Hypothalamus for Treatment of Chronic Intractable Cluster Headaches: First Reported Series

To describe the results of deep brain stimulation of the ipsilateral posterior hypothalamus for the treatment of drug-resistant chronic cluster headaches (CHs). A technique for electrode placement is reported. Because recent functional studies suggested hypothalamic dysfunction as the cause of CH bouts, we explored the therapeutic effectiveness of posterior hypothalamic stimulation for the treatment of CHs. Five patients with intractable chronic CHs were treated with long-term, high-frequency, electrical stimulation of the posterior hypothalamus. Electrodes were stereotactically implanted in the following position: 3 mm behind the midcommissural point, 5 mm below the midcommissural point, and 2 mm lateral to the midline. Since this treatment, all five patients continue to be pain-free after 2 to 22 months of follow-up monitoring. Two of the five patients have remained pain-free without any medication, whereas three of the five required low doses of methysergide (two patients) or verapamil (one patient). No adverse side effects of chronic, high-frequency, hypothalamic stimulation have been observed, and we have not encountered any acute complications resulting from the implant procedure. There have been no tolerance phenomena. These preliminary results indicate a role for posterior hypothalamic stimulation, which was demonstrated to be safe and effective, in the treatment of drug-resistant chronic CHs. These data point to a central pathogenesis for chronic CHs.

The role of the posterior hypothalamus in controlling the paradoxical phase of sleep

Chronic experiments were performed on seven cats to study the effects of high-frequency electrical stimulation of the posterior hypothalamic area on the characteristics of paradoxical sleep; the excitability of this structure at different stages of paradoxical sleep was determined. These studies showed that at the stage showing ECoG desynchronization and phasic events (stage 1), the response threshold for behavioral arousal resulting from stimulation of posterior hypothalamus was 20-30% higher than at the stage characterized by alpha-like activity in the ECoG and the absence of phasic phenomena (stage 2). Transient stimulation of the posterior hypothalamus at stage 1, at a level which was subthreshold for arousal from this state, led to a transition to stage 2 or a reduction in phasic events in paradoxical sleep without altering the qualitative characteristics of phase 1. Stimulation of the posterior hypothalamus at a level subthreshold for arousal from stage 2 and applied continuously during paradoxical sleep led to a reduction in the duration of this stage by 25-50% and to an increase in the proportion of stage 2 in the structure of paradoxical sleep. These results provide evidence that the posterior hypothalamus is involved in the inhibitory control of the 'executive' mechanisms of paradoxical sleep responsible for the ECoG desynchronization and the phasic manifestations of this state. It is suggested that the functional activity of the posterior hypothalamus at stage 1 also increases at stage 2, thus evidently fulfilling a 'guard' function.

Hippocampal Formation Theta Activity and Movement Selection

ODDIE, S. D., B. H. BLAND. Hippocampal formation theta activity and movement selection. NEUROSCI BIOBEHAV REV 22(2), 221–231, 1998.—Hippocampal theta activity results from activation in the ascending synchronizing system. It occurs during sensory/signal processing prior to and coincident with voluntary movements in mammals. The experiments summarized here suggest that it is involved in the organization of motor behaviour. (1) Procaine (a local anaesthetic) infused into the medial septum (MS) abolishes hippocampal theta activity and running behaviour elicited by electrical posterior hypothalamic (PH) stimulation. This indicates that movement elicited by PH stimulation, is dependent on ascending hypothalamo-septal circuitry. (2) Theta can also be recorded in immobile rats prior to the initiation of lateral dodging movements they make in response to conspecific rats attempting to steal their food. Following infusion of atropine into the MS, theta recorded during immobility is abolished and the rats are severely impaired at initiating movements in defence of their food. It is suggested that atropine-sensitive theta is involved in the initiation of movements made by rats in response to sensory stimuli. (3) Rats with fimbria–fornix transections were also less likely to engage in lateral dodging movements in defence of their food, were hyperactive, less thigmotaxic, and defecated more often, compared to control animals. Depth profile analysis of hippocampal field activity in lesioned animals revealed an absence of theta during electrical or chemical pons stimulation. These findings provide evidence that these neural systems are involved in signal processing relevant to movements underlying adaptive behaviour.

Hippocampal formation is involved in movement selection: evidence from medial septal cholinergic modulation and concurrent slow-wave (theta rhythm) recording

Hippocampal rhythmical slow-wave field activity which occurs in response to sensory stimulation is predominantly cholinergic (atropine-sensitive theta rhythm), can precede movement initiation, and co-occurs during non-cholinergic theta rhythm associated with ongoing movement (atropine-resistant). This relationship suggests that theta rhythm plays some role in movement control. The present naturalistic experiments tested the idea that atropine-sensitive theta rhythm plays a role in sensory integration and planning required for initiating appropriate movements. One of a pair of hungry rats, the victim, implanted with hippocampal field recording electrodes, a septal injection cannula, and a posterior hypothalamic stimulating electrode, was given food which the other, the robber, tries to steal. Since the victim dodges from the robber with a latency, distance, and velocity dependent upon the size of the food, elapsed eating time, and proximity of the robber, the movement requires sensory integration and planning. Although eating behavior seemed normal, atropine-sensitive theta rhythm and dodging were disrupted by an infusion of a cholinergic antagonist into the medial septum. When the victim in turn attempted to steal the food back, Type 1 theta rhythm was present and robbery attempts seemed normal. Prior to cholinergic blockade, posterior hypothalamic stimulation produced theta rhythm and dodges, even in the absence of the robber, but following injections, atropine-sensitive theta rhythm and dodging were absent as the animals dropped the food and ran. The results provide the first evidence to link atropine-sensitive theta rhythm and hippocampal structures to a role in sensory integration and planning for the initiation of movement.

Posterior hypothalamic control of rabbit tracheal tension and involvement of central histaminergic neurons

The hypothalamus is involved in the control of the cardiovascular system, but airway tone is less well defined. In the posterior hypothalamus, histaminergic neuronal cell bodies are located. Effects of electrical stimulation in the posterior hypothalamus on tracheal tension and the cardiovascular system were examined in anesthesized, paralyzed and artificially ventilated rabbits. Tracheal tension was determined from pressure exerted on a balloon inserted in the trachea and measured by a pressure transducer. Electrical stimulation of the posterior hypothalamus caused tracheal tension to decrease, arterial blood pressure to increase, and mild tachycardia followed by bradycardia. The tracheal tension decrease induced by posterior hypothalamic stimulation was not affected by atropine nor by transection of either the superior laryngeal nerve or the vagus nerve, but was depressed by adrenoceptor blockade. Tracheal tension decrease was also reduced by pyrilamine, a histamine H 1-receptor antagonist, administered into the fourth ventricle, but was not affected by cimetidine, a histamine H 2-receptor antagonist. The stimulation sites where these effects were evoked were interspersed among the loci of histamine immunoreactive cell bodies previously reported. Results suggest that posterior hypothalamic neurons decrease tracheal tension through the sympathetic nervous system, and involve the histaminergic neurons in this route.

Central cholinergic modulation of the exercise pressor reflex in anesthetized cats

Effects of central administration of a cholinesterase inhibitor, physostigmine, on cardiovascular responses to static contraction and passive stretch of the triceps surae were studied using anesthetized cats. Contraction increased mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) by 44 +/- 5 mmHg, 18 +/- 1 beats/min, and 86 +/- 6%, respectively. MAP, HR, and RSNA increased during stretch by 44 +/- 5 mmHg, 15 +/- 1 beats/min, and 61 +/- 4%, respectively. Administration of physostigmine (100 micrograms; 5 microliters) into the third ventricle decreased resting MAP by 22 +/- 3 mmHg and RSNA by 32 +/- 4%, with no effect on HR. Physostigmine attenuated the contraction-evoked responses as MAP, HR, and RSNA increased by 17 +/- 2 mmHg, 3 +/- 1 beats/min, and 31 +/- 6%, respectively. Also, physostigmine blunted MAP, HR, and RSNA responses to stretch (16 +/- 2 mmHg, 4 +/- 1 beats/min, and 9 +/- 6%, respectively). Posterior hypothalamic stimulation increased MAP by 39 +/- 3 mmHg, which was unaffected by physostigmine, despite a lower baseline. Cardiovascular and RSNA responses to contraction and stretch returned to control 90-120 min after physostigmine. Preadministration of the muscarinic antagonist, atropine sulfate (100 micrograms; 5 microliters), blocked the effects of physostigmine. Results suggest central cholinergic stimulation can inhibit the exercise pressor reflex in anesthetized cats.