Effects Of P-chlorophenylalanine Research Articles

Effects of p-chlorophenylalanine on time of neuronal origin during embryo-genesis in the rat

Effects of p-chlorophenylalanine on time of neuronal origin during embryo-genesis in the rat

The failure of p-chlorophenylalanine to affect voluntary alcohol consumption in rats.

1 The effects of p-chlorophenylalanine (PCPA) administered orally and intraperitoneally on rat brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content were compared. The depletion of brain 5-HT and 5-HIAA following PCPA (316 mg/kg) injected intraperitoneally every third day was not significantly different from that following the administration of PCPA (316 mg/kg) by stomach tube on eight consecutive days. 2 Rats tested for alcohol preference before, during and after treatment with PCPA on two intraperitoneal dose regimens (either 316 mg/kg then 100 mg/kg four days later or 316 mg/kg three times at intervals of three days) showed no reduction in voluntary alcohol consumption. 3 The results indicated that depletion of brain 5-HT and 5-HIAA is not responsible for the reduction of voluntary alcohol intake which has been reported to follow chronic oral administration of PCPA to the rat (Myers & Veale, 1968). The possibility of a learned aversion to alcohol due to an association with PCPA administration is discussed.

In vivo inhibition of rat liver phenylalanine hydroxylase by p-chlorophenylalanine and esculin : Experimental model of phenylketonuria

The effect of p-chlorophenylalanine ( p-CPA) and esculin on the rat liver phenylalanine hydroxylase activity have been investigated. Results have demonstrated that both compounds are good inhibitors of the enzyme in vivo, the p-CPA being the strongest, and that esculin reinforces the inhibition produced by the former when both are administered together. l-Phenylalanine administration to rats treated with p-CPA plus esculin results in an enhancement of the levels of liver phenylalanine and its metabolites, which reach values similar to those found in tissues of phenylketonuric patients while tyrosine concentrations remain near the control values. All these results suggest that the use of the p-CPA plus esculin combination supplies an improved experimental model of phenylketonuria, which can be useful for biochemical studies.

The Effect of P-Chlorophenylalanine on the Action of Potassium Ions on Mytilus Cilia

The cilioexcitatory effects of 5-hydroxytryptamine(5-HT) has been observed in Mytilus. Its presence has been demonstrated by photofluorometry, bioassay and paper chromatography. Enzymes have been proved to exist not only for the biosynthesis of 5-HT, but also for its oxidation. The evidence thus far indicates that 5-HT is the principal endogenous cilioexcitatory substance involved in the nervous control of ciliary activity in the gill of Mytilus. The available evidence suggests that the decrease in 5-HT after administration of p-chlorophenylalanine(PCPA) is mediated by a decrease in the synthesis of 5-HT resulting from an inhibition of the rate limiting enzyme, tryptophan hydroxylase. Investigators propose that PCPA is incorporated into tryptophan hydroxylase at or near the active site and is responsible for the irreversible inhibition which persists for several days. The present study investigates the effect of PCPA on potassium(K) enhancement of ciliary activity.

The effect of lowering the serotonin content of the rat brain on spontaneous locomotor activity.

Electrothermic lesions of the midbrain of rats were made in the region of the median or median plus dorsal raphe nuclei through an unipolar electrode. Concentration of serotonin (5HT) in the telencephalon decreased variously among rats and locomotor activity increased following lesions. No close correlation was obtained between locomotor activity and the 5HT concentration in the telencephalon 7 to 14 days after the lesion. The effect of p-chlorophenylalanine (PCPA, a total dose of 400 mg/kg, i.p.) was also investigated on locomotor activity, and on 5HT and 5-hydroxyindoleacetic acid (5HIAA) levels in the telencephalon of the rat. PCPA lowered the 5HT content to less than 35% of the control in the telencephalon, but did not significantly alter locomotor activity. Only an excess mounting behavior was observed. These results suggest that an increase in locomotor activity due to raphe lesion has no primary connection with lowering the 5HT content of the rat brain.

Effect of p-chlorophenylalanine on the acquisition of tolerance to ethanol and pentobarbital.

Rats were rendered tolerant to ethanol or pentobarbital by daily oral administration. Motor impairments after test doses of ethanol or pentobarbital were measured prior to and at various times during chronic treatment in order to assess the degree of tolerance development. Chronic administration of p-chlorophenylalanine (p-CPA) in a dosage regimen which produced and maintained approximately 95% depletion of brain serotonin (5-HT) did not alter motor impairment after initial acute administration of ethanol or pentobarbital. However, the rate of tolerance development to the motor-impairing effects of both drugs was slowed down in p-CPA-treated rats, p-CPA did not appear to exert this effect by altering the disposition of ethanol or pentobarbital, since blood levels determined 20 min after administration of the test doses were similar in animals treated with p-CPA and in controls. These findings suggest that brain 5-HT may have a role in tolerance development to ethanol and pentobarbital.

Effects of P-chlorophenylalanine (PCPA) on avoidance conditioning in guinea pigs

Summary The activity on avoidance behavior of p-chlorophenylalanine (PCPA) has been investigated in guinea pigs. P-chlorophenylalanine depresses avoidance responses; the results are discussed especially in connection to the problem of neurochemical transmitters in brain and their relationship to behavior.

Effect of p-chlorophenylalanine and L-phenylalanine on deoxyribonucleic acid and protein content of developing rat cerebellum

Effect of p-chlorophenylalanine and L-phenylalanine on deoxyribonucleic acid and protein content of developing rat cerebellum

Effects of p-chlorophenylalanine, α-methyl-p-tyrosine, morphine and chlorpromazine on prostaglandin E 1 hyperthermia in the rabbit

Prostaglandin E 1 (PGE 1) has been proposed as the mediator of pyrogen fever. Pyrogen fever has been shown to be enhanced in rabbits pretreated with p-chlorophenylalanine (p-CPA) but depressed in animals pretreated with α-methyl-p-tyrosine (α-MPT). In the present study α-MPT paradoxically enhanced the onset of hyperthermia produced by PGE 1 (5.0 μg) injected into a lateral ventricle. However PGE 1 hyperthermia was not affected by pretreatment with p-CPA, chlorimipramine HCl (5 mg/kg i.v.) or methysergide bimaleate (1 mg/kg i.v.). PGE 1 (0.5 μg) hyperthermia was not altered by either α-MPT or p-CPA pretreatment. These results suggest that if PGE 1 is the mediator of pyrogen fever in the rabbit, the biogenic amines exert their effects prior to the release of PGE 1. Morphine sulphate (10 mg/kg i.v.) and chlorpromazine HCl (5 mg base/kg i.v.) blocked PGE 1 hyperthermia whereas benztropine mesylate (0.2 mg/kg i.v.) was ineffective as an antagonist.

Lack of copulatory behaviour in male castrated rats after p-chlorophenylalanine.

1 The effect of p-chlorophenylalanine (PCPA) on the copulatory behaviour of normal and castrated male rats with females in oestrus was studied.2 Castration 2 months before the experiment completely prevented the increased copulatory behaviour produced by PCPA in normal rats.3 The administration of testosterone restored the copulatory behaviour in the castrated rats indicating that testosterone is essential for this behaviour.

Role of brain monoamines in male sexual behavior

Publisher Summary This chapter describes the role of brain monoamines in male sexual behavior. The effects of p-chlorophenylalanine (PCPA) administration on the homo- and heterosexual behavior are suppressed in rats, rabbits and cats by 5-hydroxytryptophan, the direct precursor of serotonin. This amino acid also abolishes the spontaneous copulatory behavior of normal rats with receptive females. This inhibition is potentiated by inhibitors of extracerebral decarboxylase, suggesting that 5-HTP acts centrally. The monoamineoxidase inhibitor, pargyline, suppresses the spontaneous copulatory behavior of male rats with receptive females at the time when brain serotonin is maximally increased and inhibition, as well as serotonin accumulation, is prevented by PCPA. Marked homosexual mounting behavior has been observed in male rats after other treatments that lower brain serotonin, such as p-chloro-N-methyl-amphetamine and the intraventricular injection of 5,6 dihydroxytryptamine and furthermore, in testosterone-treated male rats, after different inhibitors of serotonin receptors such as mesorgydine, methysergide and Wa 335-BS . Inhibition of heterosexual copulatory behavior has been observed after the administration of LSD which is considered a direct stimulant of central serotonin receptors.

The effect of p-chlorophenylalanine on forebrain tryptophan hydroxylase in rats with lesions in the raphe nucleus

The effect of p-chlorophenylalanine on forebrain tryptophan hydroxylase in rats with lesions in the raphe nucleus

The effects of p-chlorophenylalanine on morphine analgesia, tolerance and dependence development in two strains of rats

The effects of p-chlorophenylalanine (p-CPA; 100 mg/kg/day for 3 days) on morphine analgesia and the development of tolerance and physical dependence were investigated in Sprague-Dawley (SD) and Fisher (F) strains of albino rats. Using a modified flinch-jump method to detect changes in reactivity to electric footshock, F strain rats were more reactive to the footshock than SD rats, but showed less relative increase in threshold (analgesia) than SD rats following various doses of morphine. Pretreatment with p-CPA attenuated significantly morphine analgesia in SD, but not F rats. In animals implanted subcutaneously with morphine pellets, p-CPA appeared to delay the development of tolerance to morphine in both strains of rats. Hyperalgesia and loss of body weight resulted from administration of naloxone to pellet-implanted rats and p-CPA pretreatment lessened these withdrawal effects significantly in SD rats only. These results emphasize the importance of strain differences in the study of morphine analgesia and development of tolerance and dependence. Assuming differences in the function of the serotonergic inhibitory system in the two strains of rats, these data provide general support for the involvement of brain 5-HT mechanisms in modulating, if not mediating the effects of morphine.

Effect of p-chlorophenylalanine on the interaction between pbenelzine and pethidine in conscious rabbits

Effect of p-chlorophenylalanine on the interaction between pbenelzine and pethidine in conscious rabbits

Effects of P-Chlorophenylalanine on the Male and Female Sexual Behavior of Female Rats

The male and female sexual behavior of 8 testosterone-injected female rats was observed following 4 daily injections of 100mg/kg p-chlorophenylalanine. Male sexual behavior was increased while no changes were observed in female sexual behavior.

Aggressive behaviour elicited in rats by Cannabis sativa: Effects of p-chlorophenylalanine and dopa

The influence of p-chlorophenylalanine (PCPA) and dihydroxyphenylalanine (DOPA) on aggressiveness elicited by marihuana in starved rats was studied. PCPA and DOPA potentiated several-fold this behavioural manifestation; the potentiation was still greater when the animals received both drugs. On the other hand, PCPA and DOPA alone or in combination, but without marihuana, failed to elicit aggressive behaviour in starved rats. Aggressiveness did not appear when rats fed ad libitum were treated with PCPA, DOPA and marihuana. The role played by starvation, PCPA and DOPA on the capability of marihuana to induce aggressive behaviour in rats is discussed.

Effect of p-chlorophenylalanine on tryptophan hydroxylase in rat pineal.

KOE and Weissman have demonstrated that p-chlorophenylalanine (pCPA) depletes serotonin in the brain of mammals1. pCPA induces a variety of behaviour changes in rat, cat and other animals2,3, presumably because of the depletion of serotonin in the brain. The biochemical mechanism of the depletion remains, however, to be elucidated, although it has been proposed that pCPA might inactivate tryptophan hydroxylase in the brain4. We demonstrate here that pCPA does not inactivate tryptophan hydroxylase in rat pineal, although pCPA depletes the serotonin level in the pineal.

A selective effect of p-chlorophenylalanine on fixed-ratio responding.

Abstract Rats were trained to lever press for water on an FR 20 schedule of reinforcement. Administration of p-chlorophenylalanine (two injections of 150 mg/K 24 hr apart) depleted whole brain serotonin and produced marked changes in the interresponse time distribution. p-Chlorophenylalanine had no effect on the overall rate of response, or on the frequency or duration of short interresponse times. The post-reinforcement pause was reliably lengthened by p-chlorophenylalanine. The increase in post-reinforcement pause did not appear to be due to changes in the deprivation state, since an identical drug regimen had no effect on water intake, during a free watering period, in water-deprived animals. It was suggested that the effect of p-chlorophenylalanine might be due to an increase in the aversiveness of environmental stimuli.

The effect of para-chlorophenylalanine on spontaneous locomotor activity in the rat

The effect of p-chlorophenylalanine ( p-CPA), a depletor of serotonin, on spontaneous locomotor activity was investigated in rats. It was found that p-CPA induced large and reproducible increases in locomotor activity in a variety of situations. This hyperactivity could be reversed by 5-hydroxytryptophan, a precursor of serotonin. The heightened behavioral arousal was not simply a reflection of the insomnia known to be produced by p-CPA, since hyperactivity occurred during both phases of the normal diurnal cycle and because baseline activity returned to normal at different rates depending upon the type of behavioral measure used. It is suggested that one function of serotonin is to modulate arousal thresholds and that the hyperactivity following p-CPA was due to a decrease in these thresholds.

The effects of p-chlorophenylalanine on behavior: III. facilitation of brightness discrimination in satiated rats

Rats, maintained with food and water available ad lib. , learned a brightness discrimination with saccharin as the reward. Half of the subjects were injected every third day with p-chlorophenylalanine (PCPA) in Steroid Suspending Vehicle and half with the vehicle only. Facilitation of learning by PCPA was found. In a second experiment, no differences were found in acceptance of successively more concentrated solutions of quinine hydrochloride between water deprived rats injected with PCPA, and those injected with the vihicle only. It was concluded that facilitation of brightness discrimination by PCPA is not dependent upon the use of water deprived subjects, and occurs under conditions of both moderately high and low motivation.