Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “HYPOTHALAMUS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed2001

Mechanisms of ovarian steroid regulation of norepinephrine receptor-mediated signal transduction in the hypothalamus: implications for female reproductive physiology.

In many mammalian species, the ovarian steroid hormones estradiol (E(2)) and progesterone (P) act in the hypothalamus and preoptic area to coordinate the timing of female sexual receptivity with ovulation. We study lordosis behavior, an important component of sexual receptivity in rats, and its regulation by E(2) and P as a model system for understanding how hormonal modulation of synaptic neurotransmission influences reproductive physiology and behavior. Our findings suggest that E(2) and P extensively regulate synaptic communication involving the catecholamine norepinephrine (NE) in the hypothalamus. Estrogen priming shifts the balance of postsynaptic NE receptor signaling in the hypothalamus and preoptic area away from beta-adrenergic activation of cAMP synthesis toward alpha(1)-adrenergic signaling pathways. Attenuation of beta-adrenergic signal transduction is achieved by receptor-G-protein uncoupling, apparently due to stable receptor phosphorylation. E(2) modification of alpha(1)-adrenergic signaling includes both increased expression of the alpha(1B)-adrenoceptor subtype and a dramatic, P-induced reconfiguration of the biochemical responses initiated by agonist activation of alpha(1)-adrenoceptors. Among these is the emergence of alpha(1)-adrenergic receptor coupling to cGMP synthesis. We also present evidence that estrogen promotes novel, functional interactions between insulin-like growth factor-1 (IGF-1) and alpha(1)-adrenergic receptor signaling in the hypothalamus and preoptic area. Thus, estrogen amplification of signaling mediated by alpha(1)-adrenoceptors is multifaceted, involving changes in gene expression (of the alpha(1B)-adrenoceptor), switching of receptor linkage to previously inactive intracellular pathways, and the promotion of cross talk between IGF-1 and NE receptors. We propose that this hormone-dependent remodeling of hypothalamic responses to NE maximizes reproductive success by coordinating the timing of the preovulatory release of gonadotropins with the period of behavioral receptivity in female rodents.

Animals↗
PubMed1994

Expression of epidermal growth factor receptor changes in the hypothalamus during the onset of female puberty.

Recent findings have led to the concept that transforming growth factor alpha (TGF alpha) contributes to the neuroendocrine regulation of female puberty by stimulating the release of luteinizing hormone-releasing hormone (LHRH), the neurohormone controlling sexual development. It was postulated that this effect is mediated by epidermal growth factor receptors (EGFR) and that EGFR may not be located on LHRH neurons, so that TGF alpha-induced LHRH release would require an intermediate cell-to-cell interaction, presumably of glial-neuronal nature. The present study was undertaken to characterize the presence of EGFR in rat hypothalamus and to determine if changes in EGFR gene expression and EGFR protein occur at the time of puberty. RNA blot hybridization demonstrated that the hypothalamus expresses all mRNA species known to encode EGFR. RNase protection assays revealed that alternative splicing of the EGFR primary mRNA transcript occurs in the hypothalamus and produces a predominant transcript encoding the full-length EGFR and a much less abundant, shorter mRNA encoding a truncated, and presumably secreted form of EGFR. EGFR-like immunoreactive material was found in several hypothalamic regions including the organum vasculosum of the lamina terminalis, supraoptic, suprachiasmatic, and paraventricular nuclei, ependymal cells lining the third ventricle, some astrocytes associated with blood vessels, astrocytes of the pial surface, and tanycytes and glial cells of the median eminence (ME). Low levels of EGFR mRNA were detected by hybridization histochemistry in cells of the same areas containing EGFR-like immunoreactivity. Double-immunohistochemistry revealed that even though LHRH neurons are in close proximity to EGFR-positive cells, they do not contain EGFR. In the ME, EGFR-immunonegative LHRH nerve terminals tightly coexist with EGFR-positive cells, presumably tanycytes and glial astrocytes. EGFR mRNA levels measured by quantitative reverse transcription-polymerase chain reaction assay (RT-PCR) in the ME-arcuate nucleus region at the time of puberty decreased in the morning of the first proestrus, i.e., preceding the first preovulatory surge of gonadotropins, and rebounded at the time of the surge. Functional EGFR protein levels, detected by the ability of the receptor to autophosphorylate in response to ligand or divalent antibody-induced activation, changed in a similar manner at the time of puberty. No such changes were observed in the cerebellum, a brain region irrelevant to neuroendocrine reproductive control. These results demonstrate the existence of EGF receptors in the prepubertal female rat hypothalamus and suggest that changes in EGFR gene expression and biologically active EGFR protein contributes to the neuroendocrine process underlying the first preovulatory surge of gonadotropins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Release of endogenous GABA in the posterior hypothalamus of the conscious rat; effects of drugs and experimentally induced blood pressure changes.

Push-pull superfusion was used to investigate the release of endogenous GABA in the posterior hypothalamus of the conscious, freely moving rat at basal conditions and in response to centrally applied drugs or to peripherally induced blood pressure changes. After an initial, exponential decline, the release rate of GABA remained fairly constant for many hours. Fluctuations in the release rate of GABA point to the existence of an ultradian rhythm with an approximate frequency of 1 cycle/65 min. Hypothalamic superfusion with a potassium-rich (50 or 90 mmol/l) artificial cerebrospinal fluid led to a concentration-dependent increase in the GABA release. The release of GABA was also enhanced by veratridine (1 or 10 mumol/l) in a concentration-dependent way. Hypothalamic superfusion with the neutrotoxin tetrodotoxin (1 mumol/l) led to a long-lasting decrease in the GABA release. The rise in blood pressure (45 mmHg) elicited by an intravenous infusion of noradrenaline was associated with an increased release rate of GABA in the hypothalamus. Hypotension produced by nitroprusside (25 mmHg) led to a counteracting decrease in hypothalamic GABA outflow. The findings suggest that approximately 45% of the basal outflow of GABA found in the superfusate are released from GABA-ergic neurons of the posterior hypothalamus. The release rate of GABA fluctuates according to an ultradian rhythm. The modified release of GABA in response to experimentally induced blood pressure changes suggests that, in the posterior hypothalamus of the conscious rat, GABAergic neurons are involved in cardiovascular control and possess a hypotensive function.

Animals↗
PubMed1993

Modulation by dopamine receptors of the histamine release in the rat hypothalamus.

The involvement of dopaminergic neurons of the hypothalamus in the modulation of histamine release was studied by the push-pull technique. The posterior hypothalamus of the conscious, freely moving rat was superfused with artificial cerebrospinal fluid (CSF) and the release of histamine was determined radioenzymatically in the superfusate. Agonists and antagonists of dopamine D1-, D2- and D3-receptors were dissolved in CSF and applied to the hypothalamus through the push-pull cannula. Hypothalamic superfusion with the D1-, D2- and D3-receptor agonists dopamine or R(-)-apomorphine enhanced the release rate of histamine. (+/-)-Apomorphine also enhanced the release of histamine, but to a lesser extent than did equimolar concentration of R(-)-apomorphine. The D3-agonist quinpirole inhibited the release of histamine, while the D1-receptor agonist SKF 82958 [(+-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine] did not virtually influence the release of the neurotransmitter. On the other hand, [-]-sulpiride which predominantly blocks D2-receptors, decreased histamine release. Hypothalamic superfusion with SKF 83566 [(+-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine], which seems to be a selective antagonist of D1-receptors, enhanced the release rate of histamine. These findings suggest that dopaminergic neurons of the hypothalamus influence the release of histamine from its neurons in a dual way. D2-heteroreceptors stimulate the release of histamine, while D3-heteroreceptors seem to inhibit the release of this neurotransmitter. Both types of dopamine receptors might be located presynaptically on histaminergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Release of endogenous acetylcholine in the hypothalamus of conscious rats.

The release of endogenous acetylcholine was investigated by the push-pull technique. The posterior hypothalamus of conscious rats was superfused through a push-pull cannula with artificial cerebrospinal fluid (ACSF) which contained 1 mumol/l neostigmine. Acetylcholine was determined in the superfusate by high pressure liquid chromatography and electrochemical detection. Hypothalamic superfusion with potassium-rich (100 mmol/l) ACSF led to a pronounced increase in the release rate of acetylcholine. Tetrodotoxin (1 mumol/l) almost abolished the basal release of the neurotransmitter. Superfusion of the hypothalamus with atropine (10 or 50 mumol/l) led to a concentration-dependent increase, whereas superfusion with oxotremorine (50 mumol/l) inhibited the release rate of acetylcholine. It is concluded that acetylcholine released into the superfusate of the hypothalamus originates from cholinergic neurons. Furthermore, the release of acetylcholine seems to be modulated by muscarinic acetylcholine receptors, probably located on cholinergic neurons of the hypothalamus.

Acetylcholine↗
PubMed1980

The effect of electrical stimulation in the hypothalamus on the monosynaptic jaw closing and the disynaptic jaw opening reflexes in the cat.

The effects of electrical stimulation in the hypothalamus on the monosynaptic jaw closing and the disynaptic jaw opening reflexes were investigated in cats anaesthetized with chloralose. The hypothalamic electrodes were located by observation of behavioural attack responses in the unanaesthetized animal and by means of Horsley-Clarke coordinates. The locations were verified in histological serial sections. Hypothalamic conditioning with trains of 3--10 pulses, 0.5 ms duration, 0.5 mA, 500 Hz, evoked a strong facilitation of the jaw closing reflex and a facilitation followed by an inhibition of the jaw opening reflex. These effects differed from those elicited from the cerebral cortex. The hypothalamic effects had a longer latency (11--13 ms) and required a longer train of conditioning stimuli than was the case with those evoked from the cortex. Bilateral ablation of the sensorimotor cerebral cortex or lesion of the pyramids at the lower pontine level diminished but did not abolish the hypothalamic effects. They did, however, disappear after lesions including the ventral midbrain tegmentum. The stimulus positions eliciting the largest hypothalamic effects on the jaw reflexes were located in a region extending medio-laterally from the perifornical area to the entrance of the ansa lenticularis in the lateral hypothalamus. Rostro-caudally the location was found at the level of the ventromedial hypothalamic nucleus and the anterior hypothalamus just rostral to this nucleus. The region corresponds to those parts of the hypothalamus from which agonistic and feeding responses have been evoked. It is suggested that the observed hypothalamotrigeminal mechanism may exercise a tonic influence on the trigeminal motoneurones, thereby controlling the set point of the biting force. The implications of this hypothesis on the etiology of bruxism and the myofascial pain dysfunction are discussed.

Animals↗
PubMed1979

In vivo release of endogenous catecholamines in the hypothalamus.

The posterior hypothalamus of anaesthetized cats was superfused with a push-pull cannula and the release of the endogenous catecholamines noradrenaline, adrenaline and dopamine was determined in the superfusate. The rate of release of the three catecholamines followed an ultradian rhythm, the time interval between two adjacent phases of high rate of release being about 70 min. Pretreatment of the animals with reserpine decreased the levels of catecholamines in the hypothalamus and rest of the brain and reduced their rate of release into the superfusate. Hypothalamic superfusion with superfusing fluid of high concentration of potassium and low concentration of sodium enhanced the rate of release of noradrenaline and adrenaline; this effect was abolished when the hypothalamus was superfused with calcium-free solution. Electrical stimulation of the locus coeruleus ipsilateral to the superfused hypothalamus increased the release of noradrenaline and adrenaline, stimulation of the contralateral locus coeruleus enhanced the release of noradrenaline, adrenaline and dopamine. In both cases, the rate of release of adrenaline was enhanced to a lesser extent than the rate of release of noradrenaline. The release of noradrenaline and adrenaline was increased to a higher extent on stimulation of the ipsilateral locus coeruleus than on stimulation of the contralateral one.

Animals↗
PubMed1978

Central thermosensitivity in conscious goats: hypothalamus and spinal cord versus residual inner body.

Experiments were performed on conscious goats to confirm the suggestion that in this species the inner body contains more thermosensitive structures than those residing in the hypothalamus and spinal cord. For this purpose goats were chronically implanted with local thermodes and intravascular heat exchangers to allow independent temperature control of the hypothalamus, spinal cord and residual inner body. With the hypothalamus and spinal cord clamped simultaneously at different levels between 32 degrees C and 40 degrees C, residual internal temperature was lowered by subtracting heat via the intravascular heat exchanger. The residual internal temperature at which shivering and increased heat production occured due to heat extraction, was directly related to the value of the combined hypothalamic and spinal cord clamp temperature. The higher hypothalamic and spinal cord clamp temperatures were, the lower residual internal temperature fell before shivering occurred and heat production rose. Plots relating residual internal temperature to hypothalamic and spinal cord temperature at different levels of heat production showed the signal input generated within the residual inner body to be of nearly the same order of magnitude as that from the hypothalamus and spinal cord.

Animals↗
PubMed1978

Acid proteinase of hypothalamus. Purification, some properties, and action on somatostatin and substance P.

In a continuing study of the physiological role of protein breakdown in the hypothalamus, acid proteinase from bovine hypothalamus was purified about 1000-fold. The molecular weight of the enzyme was approximately 50,000. Masimal activity against hemoglobin was obtained at pH 3.2-3.5; serum albumin was split much more slowly. Hypothalamus acid proteinase was partially inhibited by beta-phenyl pyruvate, or benzethonium Cl, and was completely inhibited by low concentrations of pepstatin. This proteinase splits somatostatin, substance P, and analogs of substance P. The probable sites of enzyme action on these peptides were determined by the end group dansyl technique. The enzyme, most likely cathepsin D, may play an important role in the formation and breakdown of peptide hormones in the hypothalamus.

Animals↗
PubMed1985

Postnatal ontogeny of uridine kinase in the cerebellum, hypothalamus, and cerebral cortex of the rat.

Postnatal developmental patterns of uridine kinase were determined in crude subcellular fractions of the rat cerebellum, hypothalamus and cerebral cortex at ages 3 through 60 days. The highest specific activity and predominant distribution of enzyme was in the 105,000 g supernatant of the 3 brain regions. Enzyme activity in hypothalamus and cerebral cortex was maximum at 3 days and decreased with age; in cerebellum it increased through 13 days and decreased thereafter. Thus, the pattern of activity in hypothalamus and cerebral cortex paralleled changes in DNA and RNA synthesis through age 60 days; in cerebellum, it more closely approximated changes in DNA synthesis during early development. Changes in Km with aging suggest that the brain regions contain more than one form of enzyme. The highest particulate activity was in the microsomal fraction of the cerebellum and hypothalamus at all ages and in the cortex at 35 and 60 days. Relative specific activity for microsomal fractions of the brain regions at 60 days indicate a concentration of the enzyme which may be relevant in the maintenance of RNA activity in adult brain.

Age Factors↗
PubMed1994

In vitro TRH release from hypothalamus slices varies during the diurnal cycle.

We have previously described a daily rhythm in thyrotropin releasing hormone (TRH) and TRH mRNA in the rat hypothalamus. To determine whether TRH release fluctuates in a diurnal manner, we have measured basal and potassium stimulated release from hypothalamic slices, and compared it to release from olfactory bulb slices, during the diurnal cycle. Basal TRH release was higher at 7:00 h than at any other time (1:00, 13:00 or 19:00 h) in either hypothalamus or olfactory bulb. The ratio of stimulated over basal release was higher in the hypothalamus at 19:00 h, when TRH content was highest. Potassium stimulated TRH release from olfactory bulb was not different from basal release at any time. TRH release fluctuations were not due to a rhythm of extracellular inactivation: the activity of pyroglutamyl aminopeptidase II, an ectoenzyme responsible for TRH inactivation, was constant throughout the cycle. Our data demonstrate that diurnal variations of TRH release occur in vitro and that the enhanced responsiveness to potassium stimulation in hypothalamus is correlated with increased levels of peptide.

Aminopeptidases↗
PubMed1990

In vivo 5-HIAA release from the anterior hypothalamus in the ovariectomized and estradiol treated rat following perfusion with progesterone.

In the present study the frequency and magnitude of the release of 5-Hydroxyindoleacetic Acid (5-HIAA) was measured from the anterior hypothalamus of ovariectomized (OVX) and OVX rats treated with estradiol (E2). Female, Holtzman strain rats were maintained on a photoperiod of 14 H light from 0100 to 1500 H and experiments performed from 0900 to 1700 H. Animals exhibiting four-day estrous cycles (250-300 gms) were OVX (20 days recovery) and a push-pull-cannula (PPC) implanted and stereotaxically aimed at the SCN region in the anterior hypothalamus. Following a 7-10 day recovery push-pull-perfusion (PPP) experiments were performed on either OVX females or on OVX females in which a silastic E2 implant (150 micrograms E2/ml. sesame oil), was placed sc 48 H prior to PPP. In other experiments progesterone (P4) was perfused in a pulsatile manner over the SCN region of the anterior hypothalamus. The overall average 5-HIAA release in the OVX treated rats (548 +/- 358 pg/10 min.) was similar to that in the OVX E2 group (694 +/- 148 pg/10 min). The average period of 5-HIAA release was (48.2 +/- 5.5 min) in the OVX group and (56.0 +/- 9.8 min) in the OVX E2 group. These results indicate that exposure of long term OVX rats (20 days) to E2 has no effect on the release or period of 5-HIAA release from serotonergic terminals concentrated in the SCN of the anterior hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Evoked responses of pyramidal tract neurons to stimulation of the lateral hypothalamus.

The evoked responses of identified pyramidal tract neurons of the pericruciate region of the cortex arising on stimulation of the posterior, tuberal, and anterior sections of the lateral hypothalamus were investigated in acute experiments on cats anesthetized with chloralose. THe pyramidal tract neurons recorded were situated at a depth of 0.75-2.5 mm and on stimulation of the hypothalamus discharged with a latent period of 1.6-52.5 msec. They discharged most efficiently in the case of stimulation of the caudal half of the lateral hypothalamus. The pyramidal tract neurons activated by the hypothalamus were also tested by electrocutaneous stimulation of the four limbs. Of the neurons 75% responded to stimulation of several limbs, i.e., they had a broad bilateral receptive field, while 15% reacted to stimulation of one contralateral limb (either the anterior limb or the posterior limb), i.e., they had a small contralateral receptive field. Comparison of the latent periods of the anti- and orthodromic responses of the pyramidal tract neurons did not reveal any relationship between the magnitude of the latent period of the orthodromic response (on hypothalamic or electrocutaneous stimulation) and the type of pyramidal tract neuron (according to the axonal transmission velocity). No relationship between the latent period of hypothalamic stimulation and the magnitude of the latent period of the response to a peripheral stimulus was detected either.

Animals↗
PubMedDate not supplied

Delta sleep-inducing peptide as a factor increasing the content of substance P in the hypothalamus and the resistance of rats to emotional stress.

The influence of delta sleep-inducing peptide (DSIP, 60 and 120 nmole/kg, intraperitoneally) on the content of substance P (SP) in the hypothalamus of rats was studied in male rats of the August line. It was demonstrated that the administration of DSIP significantly increases the average content of SP in the hypothalamus, as well as its content in animals resistant to and predisposed to emotional stress. A daily one-time administration of DSIP before placing the rats in conditions of stress increases the content of SP in the hypothalamus which was decreased during emotional stress. The preliminary one-time administration of DSIP to animals subjected to a stressor influence also increases the SP content in the hypothalamus. It was established that a one-time administration of DSIP in a dose of 60 nmole/kg sharply decreases the classical manifestations of stress such as the hypertrophy of the adrenals and involution of the thymus.

Adrenal Glands↗
PubMedDate not supplied

Blood-flow and pO2 in the posterior hypothalamus of cats during paradoxical sleep.

It was found in chronic experiments in cats, using the recording of local blood flow and oxygen tension (pO2) in the anterior and posterior hypothalamus in the sleep-wakefulness cycle, that when the phases of sleep are alternated, the changes in these parameters are in different directions: the level of blood flow and the frequency of fluctuation of the pO2 during paradoxical sleep increase in the posterior hypothalamus, while they decrease in the anterior hypothalamus. On the other hand, the opposite pattern is observed during slow-wave sleep. The multidirectionality of the changes in local blood flow level and in the frequency of fluctuations of pO2 in one and the same sleep phase indicate that they are of local origin and must be governed by functional-metabolic shifts in these structures; the functional state of the posterior hypothalamus during paradoxical sleep is assessed on this basis.

Animals↗
PubMed1989

Different regulation of serotonin receptors following adrenal hormone imbalance in the rat hippocampus and hypothalamus.

Adrenal influence on serotonin (5-HT) transmission in the hippocampal and hypothalamic areas was studied in adrenalectomized rats receiving or not corticosterone replacement. After adrenalectomy, the 5-HT presynaptic receptors were desensitized both in hippocampus and hypothalamus: a significant increase in 5-HT 1 and 5-HT 2 receptor binding numbers took place in membranes from the hippocampus, but not in hypothalamus, while no changes in affinity of receptors to radioligands were observed in either brain area. Corticosterone treatment restored the adrenalectomy-impaired 5-HT autoreceptor sensitivity in hippocampus and hypothalamus and 5-HT density receptor sites in the hippocampus. Serotonin autoreceptor down-regulation following adrenalectomy may increase 5-HT release to maintain the constancy of serotonergic transmission in the brain and 5-HT modulated CRH-ACTH release to compensate the plasma corticosteroid drop. Corticosterone seems to display a distinct tonic control on serotonin transmission in both hippocampus and hypothalamus, the diversity being due to the different roles played by the hormone in these brain regions.

Adrenalectomy↗
PubMed1997

Fluoxetine increases norepinephrine release in rat hypothalamus as measured by tissue levels of MHPG-SO4 and microdialysis in conscious rats.

The selective serotonin uptake inhibitor fluoxetine (10 mg/kg i.p.) increased tissue levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol sulfate (MHPG-SO4) in rat hypothalamus, indicating an increased release of norepinephrine. Microdialysis studies in conscious rats showed that fluoxetine (10 mg/kg i.p.) increased extracellular concentrations of norepinephrine as well as serotonin in the hypothalamus. In contrast, desipramine (10 mg/kg i.p.) increased extracellular concentration of norepinephrine but not serotonin in the hypothalamus. Consistent with its mechanism of being a selective serotonin uptake inhibitor, local perfusion of fluoxetine (10 microM) caused a 7-fold increase in hypothalamic extracellular serotonin and a small non-significant increase in extracellular norepinephrine. The subsequent systemic injection of fluoxetine (10 mg/kg s.c.) after local perfusion caused a 3-fold increase in extracellular norepinephrine, indicating that fluoxetine's action leading to an increase in extracellular norepinephrine was not occurring in the terminal areas of the hypothalamus but elsewhere in the brain, possibly cell bodies in the locus coeruleus.

Adrenergic Uptake Inhibitors↗
PubMed1990

The hypothalamus in MPTP-induced parkinsonism.

1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) has been shown to produce a parkinsonian syndrome in humans and other primates. Recent studies have demonstrated that in humans the hypothalamus has the highest binding density for (3H) MPTP, which corresponds to monoamine oxidase type B (MAO-B). There is evidence that the conversion of MPTP to the toxic compound MPP+ takes place in the hypothalamus; subsequently, MPP+ is transported to the striatal system, where destruction of nigrostriatal dopamine neurons occurs. Thus, the hypothalamus appears to be a primary target organ of MPTP toxicity. This assumption is supported by the observation that monkeys exposed to MPTP exhibit extensive pathological lesions in the hypothalamus which are manifested clinically by the development of life-threatening anorexia requiring forced feeding to overcome. We discuss the clinical implications of MPTP-induced hypothalamic damage to the pathophysiology of MPTP-induced parkinsonism and to Parkinson disease. It is suggested that consideration of hypothalamic involvement in MPTP-induced parkinsonism may provide a broader understanding of the pathophysiology of parkinsonism and may, in addition, account for the preliminary observations that MAO-B inhibitors retard the progression of Parkinson disease and possibly prolong life expectancy.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗