The effect of para-chlorophenylalanine on the sleep of cats

Koella, Werner P.; Feldstein, Aaron; Czicman, John S.

doi:10.1016/0013-4694(68)90158-2

Cited by 196 publications

(33 citation statements)

References 7 publications

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“…No determinations have been made of the 5-HT content of the hypothalamus in cats treated with p-chlorophenylalanine in the same way as in the present experiments -that is 3 days after an intraperitoneal injection of 300 mg/kg. Koella, Feldstein & Czicman (1968), however, found that 3 days after an intraperitoneal injection of half the dose (150 mg/kg) the 5-HT content of the cat's diencephalon was reduced to a mean of 15°,,.…”

Section: Discussionmentioning

confidence: 94%

Effect of monoamineoxidase inhibitors on 5‐hydroxytryptamine output from perfused cerebral ventricles of anaesthetized cats

Goodrich

1969

British J Pharmacology

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1. In cats anaesthetized with pentobarbitone sodium, intraperitoneal injections of four inhibitors of monoamine oxidase (MAO) were shown to increase the 5-hydroxytryptamine (5-HT) in the effluent from the perfused cerebral ventricles. 2. Weight for weight, tranylcypromine was found to be about twice as potent as pheniprazine, eight times as potent as nialamide and sixty times as potent as pargyline. 3. The effect of tranylcypromine was also examined after reserpine had been injected into the cerebral ventricles or after p-chlorophenylalanine, given intraperitoneally. In both conditions tranylcypromine retained its ability to increase the 5-HT output from the perfused cerebral ventricle, but the effect was attenuated, more after p-chlorophenylalanine than after reserpine. 4. Evidence is put forward that in both conditions the brain is not completely depleted of its 5-HT, but that the 5-HT is only reduced, more after p-chlorophenylalanine than after reserpine.Recently it was shown that an intraperitoneal injection of tranylcypromine, an inhibitor of monoamine oxidase (MAO) increased the 5-hydroxytryptamine (5-HIT) content in the effluent from the perfused cerebral ventricles of anaesthetized cats (El Hawary, Feldberg & Lotti, 1967). The increase was attributed to inhibition of the MAO. As the 5-HT released in the ventriular walls is no longer destroyed after inhibition of the enzyme it would diffuse in greater amounts into the fluid perfusing the ventricles. However, tranylcypromine has strong stimulating amphetamine-like actions which might increase the release of 5-HT. This, too, would result in an increased output in the effluent. This possibility would be excluded as the cause for the observed increase, if MAO inhilbitors without amphetamine-like actions also were to increase the 5-HT output, and if their ability to do so were related to their potency as inhibitors of MAO.In the present experiments, four inhibitors of different potency were used. Two of them, tranylcypromine and pheniprazine, have strong amphetamine-like actions,

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Section: Discussionmentioning

confidence: 94%

Effect of monoamineoxidase inhibitors on 5‐hydroxytryptamine output from perfused cerebral ventricles of anaesthetized cats

Goodrich

1969

British J Pharmacology

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“…Historically, methods to functionally deplete serotonin have been problematic. Even previous approaches that have been moderately successful in experimental animals -such as the 5-HT synthesis inhibitor, parachloro-phenylalanine (PCPA); the neurotoxin 5-6-dihydroxy-tryptamine; or various lesions to the serotonergic raphe nuclei of the brainstem -have been non-specific, rife with secondary effects, or clearly inapplicable to humans (e.g., Engelman et al 1967;Koella et al 1968;Jouvet et al 1967). The advent of rapid tryptophan depletion (RTD) as a method to deplete central serotonin has been met with enthusiasm because of its reversibil-ity, its relative lack of side effects, and its merit in elucidating the pathophysiology of various psychiatric conditions.…”

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confidence: 99%

Clinical and Physiological Consequences of Rapid Tryptophan Depletion

Moore

Landolt

Seifritz

et al. 2000

Neuropsychopharmacology

184

121

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We review here the rapid tryptophan depletion (RTD) methodology and its controversial association with depressive relapse. RTD has been used over the past decade to deplete serotonin (5-hydroxy-tryptamine, or 5-HT) in humans and to probe the role of the central serotonin system in a variety of psychiatric conditions. Its current popularity was stimulated by reports that RTD reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) KEY WORDS : 5-HT; Serotonin; Tryptophan-free drink; Major depressionSerotonin (5-hydroxy-tryptamine, or 5-HT) is involved in many physiologic and behavioral systems and clinical disease states. Much of the information available on the function of serotonin comes from pharmacological agents which mimic or amplify endogenous serotonergic neurotransmission, such as serotonin agonists or SSRIs. Historically, methods to functionally deplete serotonin have been problematic. Even previous approaches that have been moderately successful in experimental animals -such as the 5-HT synthesis inhibitor, parachloro-phenylalanine (PCPA); the neurotoxin 5-6-dihydroxy-tryptamine; or various lesions to the serotonergic raphe nuclei of the brainstem -have been non-specific, rife with secondary effects, or clearly inapplicable to humans (e.g., Engelman et al. 1967;Koella et al. 1968;Jouvet et al. 1967). The advent of rapid tryptophan depletion (RTD) as a method to deplete central serotonin has been met with enthusiasm because of its reversibil- NO . 6 ity, its relative lack of side effects, and its merit in elucidating the pathophysiology of various psychiatric conditions. This paper reviews the RTD methodology and its reported ability to induce a depressive relapse in euthymic patients, and other physiological and clinical effects. RAPID TRYPTOPHAN DEPLETION Availability of Tryptophan and Serotonin SynthesisRTD is based on the current understanding of the 5-HT biosynthetic pathway, in which the first step is generally considered to be the rate-limiting one. The first step entails the hydroxylation of the amino acid TRP (by the enzyme TRP hydroxylase, or TRP-H) into the intermediate product 5-hydroxy-tryptophan, or 5-HTP. 5-HTP is then decarboxylated into 5-HT. Under normal conditions, TRP-H is about 50% saturated with TRP. Increasing or decreasing the availability of TRP correlates highly with the amount of 5-HT produced (e.g., Lin et al. 1969;Schaechter and Wurtman 1990). Because the body cannot synthesize TRP, reducing dietary intake of TRP reduces TRP levels in plasma and diminishes its transport from plasma into the brain.In humans, TRP depletion is accomplished by consuming a TRP-free amino acid drink (e.g., Delgado et al. 1990;Biggio et al. 1974). This drink contains 15 amino acids in the same proportion as in human milk, except that TRP, aspartic acid, and glutamic acid are omitted (see Table 1). Within a matter of hours (4 to 12), plasma TRP declines to 10-50% of baseline levels (Delgado et al. 1990(Delgado et al. , 199...

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“…It is known that treatment of cats with pCPA results in total insomnia lasting for several days; during recovery, PS reappears progressively without rebound (Mouret et al, 1967). Peripheral or intraventricular administration of 5-HTP reverses pCPA insomnia (Mouret et al, 1967;Koella et al, 1968). The time course of this reversal is characteristic: 5-HTP blocks immediately pCPA-induced PGO waves and restores quiet sleep in about 30 min and PS only after 1 h. However, pCPA does not prevent the PS rebound which normally follows instrumental deprivation, but suppresses quiet sleep, thus inducing a narcoleptic syndrome in the cat.…”

Section: The Role Of Indolaminergic Neuronesmentioning

confidence: 99%

Biochemical pharmacology of paradoxical sleep.

Gaillard¹

1983

Brit J Clinical Pharma

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1 The role of noradrenergic cells in the regulation of paradoxical sleep is still controversial, and experimental data have given rise to contradictory interpretations.2 Early investigations focused primarily on chemical neurotransmissions. However, the process of information transmission between cells involves many other factors, and the cell surface is an important site for transduction of messages into modifications of the activity of postsynaptic cells.3 a-adrenoceptors are believed to play an important role in the control of wakefulness and paradoxical sleep. Experimental evidence suggests that physiological modulation of receptor sensitivity, possibly by specific neuro-modulators, may be a key mechanism in synaptic transmission. 4 In the investigation of the mechanisms involved in paradoxical sleep regulation, lesions of the locus coeruleus have given equivocal results. Collateral inhibition, probably mediated by a2-adrenoceptors, appears to be a powerful mechanism. The exact temporal relationship between noradrenergic cell activation and paradoxical sleep production is not established, but 5-HT appears to be involved. Differences between paradoxical sleep and waking may be related to a physiological modulation of a2-adrenoceptor sensitivity.

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The effect of para-chlorophenylalanine on the sleep of cats

Cited by 196 publications

References 7 publications

Effect of monoamineoxidase inhibitors on 5‐hydroxytryptamine output from perfused cerebral ventricles of anaesthetized cats

Effect of monoamineoxidase inhibitors on 5‐hydroxytryptamine output from perfused cerebral ventricles of anaesthetized cats

Clinical and Physiological Consequences of Rapid Tryptophan Depletion

Biochemical pharmacology of paradoxical sleep.

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