Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The s.c. administration of 20 mg/kg of morphine-HCl produced a decrease in the spontaneous locomotor activity (SLMA) of rats. The decrease in SLMA was significantly antagonized by p-chlorophenylalanine (p-CPA). When rats pretreated with p-CPA were given 5-hydroxytryptophan before morphine injection, the marked sedative response to morphine was restored, suggesting that the morphine-induced decrease in SLMA of rats may depend on the release of 5-hydroxytryptamine by morphine. By contrast, the s.c. administration of 5 mg/kg of morphine-HCl produced a significant increase in SLMA of rats. The magnitude of the increase was reduced by atropine, scopolamine or alpha-methyl-p-tyrosine. It appears that both adrenergic and cholinergic mechanisms participate in the increase in SLMA of rats induced by morphine. Both the increase in SLMA produced by 5 mg/kg of morphine and the decrease in SLMA induced by 20 mg/kg of morphine were completely antagonized by the s.c. administration of naloxone-HCl, 0.0625 and 0.25 mg/kg, respectively. Thus, it appears that the receptor with which morphine interacts to produce stimulation is chemically identical with or very similar to the receptor with which morphine combines to induce depression. The former receptors, however, are likely to be located on different neurons from the latter.
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PMID:Effects of humoral modulators and naloxone on morphine-induced changes in the spontaneous locomotor activity of the rat. 0 52

Endogenously depressed patients who showed an antidepressant response to the tricyclic drug imipramine continued to show sustained well being after alpha-MPT was added whereas depression returned when small doses of PCPA were added for brief periods. In one patient the antidepressant response to imipramine occurred after pre- and continued treatment with alpha-MPT. Urinary excretion levels of MHPG in one of the patients studied longitudinally did not correspond to the direction of clinical affective state but did reflect anticipated changes during alpha-MPT treatment. Implications are that serotonergic mechanisms are likely involved in the anti-depressant effects of imipramine in man.
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PMID:Use of synthesis inhibitors in defining a role for biogenic amines during imipramine treatment in depressed patients. 13 59

The responsiveness of functionally identified cat spinal dorsal horn neurons to iontophoretically applied substance P (SP) and 5-hydroxytryptamine (5-HT) has been investigated by means of extracellular recording after 5-HT depletion with p-chlorophenylalanine (p-CPA). In addition, the spinal levels of 5-HT, SP, cholecystokinin octapeptide, neurotensin, and vasoactive intestinal polypeptide have been measured in intact and p-CPA-pretreated cats. In the present study we have demonstrated an altered responsiveness of dorsal horn neurons to locally applied SP and 5-HT. We found in p-CPA-pretreated cats that the proportion of neurons responding with excitation to SP and 5-HT was significantly increased. At the same time, depression induced by 5-HT in the dorsal horn cells was virtually absent in p-CPA-pretreated animals. Our finding that spinal level of 5-HT was significantly decreased in p-CPA-treated animals is consistent with previous studies. No convincing alteration in the spinal levels of 4 analyzed peptides was found in p-CPA-treated animals. The present study has shown that pharmacological depletion of 5-HT has two major effects: (1) it increases significantly the proportion of dorsal horn neurons excited by SP and 5-HT; and (2) it is ineffective in inducing 5-HT supersensitivity. Further work is needed to explain mechanisms involved in these effects.
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PMID:Altered responsiveness to substance P and 5-hydroxytryptamine in cat dorsal horn neurons after 5-HT depletion with p-chlorophenylalanine. 242 Apr 13

The role of serotonin in the anorexic response of rats to an amino acid-imbalanced diet was investigated. After chronic depletion of serotonin with parachlorophenylalanine (PCPA, 300 mg/kg) or 5,7-dihydroxytryptamine (DHT, 200 micrograms/rat, intracisternally), initial intake of a mild isoleucine-imbalanced diet was reduced by 60% vs. a 17% reduction after saline injection. After acute treatment with the agonist, quipazine (quip, 5 mg/kg ip) or the precursor, tryptophan (TRP, 1% added to the diet), imbalanced diet intake was also exacerbated. PCPA and DHT may have caused receptor supersensitivity, such that the food intake depression after serotonin depletion was similar to that seen with the quip and TRP treatments. Injection of the autoreceptor agonist, 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT, 500 micrograms/kg sc), to reduce transmission in the serotonergic systems resulted in an attenuation of the usual food intake depression of the amino acid-imbalanced diet (only a 7%, nonsignificant reduction). Also measurements made in the absence of pharmacological treatment showed that the ratio 5-hydroxyindole acetic acid-to-serotonin, a putative index of serotonin turnover, was increased 155% in the raphe nuclei and 140% in the hippocampus 3.5 h after ingestion of the mild isoleucine-imbalanced diet. Therefore increased serotonergic activity in some brain areas may be associated with the initial depression of food intake in rats fed an imbalanced amino acid diet.
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PMID:Serotonin and feeding responses of rats to amino acid imbalance: initial phase. 244 14

The influence of drugs which modify the concentration of brain monoamines on the size of the 50% antitussive dose (AtD50) of morphine (M), dihydrocodeine (DC) and dextromethorphan (DX) was investigated in male Sprague-Dawley rats. The puncture electrode-induced cough method was used for inducing cough. The AtD50 was calculated by the "up and down" method. All drugs were injected i.p. Concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in the whole brain were measured by means of high performance liquid chromatography with electro-chemical detection. The values for the AtD50 of M, DC and DX were 1.22, 1.44, and 6.06 mg/kg, respectively. Reserpine (2.5 mg/kg/day, 2 days) produced depression of more than 80% in levels of NE, DA and 5-HT in the brain. This treatment resulted in a substantial reduction in the antitussive effect of the cough suppressants, as evidenced by an increase in the AtD50 of M, DC and DX. p-Chlorophenylalanine (PCPA; 300 mg/kg, 24 hr) specifically produced a reduction of more than 70% in the level of 5-HT in the brain. The PCPA-treated rats also displayed an inhibition of the antitussive effect. The AtD50 in reserpine- and PCPA-treated rats was 2- and 4-fold higher, respectively, than the AtD50 for normal rats. alpha-Methyl-p-tyrosine (300 mg/kg, 5 hr) produced a significant reduction in the levels of NE and DA in the brain, but the antitussive effects of M, DC and DX were not altered. These results suggest that 5-HT in the brain may play an important role in the mechanism of action of antitussive drugs.
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PMID:Monoamines and the mechanisms of action of antitussive drugs in rats. 296 57

The subacute toxic effects of cyclopiazonic acid (CPA; given orally) were characterized in the dog (CPA was purified from cultures of Aspergillus flavus). Four groups of dogs were given CPA in gelatin capsules for 90 days at the following dosage levels: 0.05, 0.25, 0.5, and 1.0 mg/kg of body weight; a 5th group was used as controls. All dogs administered the 0.5 and 1.0 mg of CPA/kg dosages and 1 dog given the 0.25 mg of CPA/kg dosage died or were humanely killed before the scheduled termination of the study. Clinical signs of intoxication appeared 2 to 44 days after dosing was started and consisted of anorexia and, in 1 to 2 days, vomiting, diarrhea, pyrexia, dehydration, weight loss, and CNS depression. Grossly, the entire alimentary tract had diffuse hyperemia with focal areas of hemorrhage and ulceration. Other lesions were renal infarcts, necrotizing epididymitis, and ulcerative dermatitis. Microscopic lesions included ulceration, necrosis, vasculitis, lymphoid necrosis, karyomegaly in several organs, and decreased mitotic activity in intestinal crypt epithelium. Ulcerative and necrotic lesions were usually associated with vascular lesions. Clinical pathologic changes were leukocytosis, neutrophilia, lymphopenia, monocytosis, and increased serum alkaline phosphatase activity.
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PMID:Cyclopiazonic acid mycotoxicosis in the dog. 392 55

The hypothesis of a serotonergic basis of reward rests partly on data showing that serotonin (5-HT) depletion by para-chlorophenylalanine (p-CPA) causes depression of self-stimulation (SS) rates. These data do not clearly demonstrate a time course relationship between 5-HT depletion and SS suppression. The present study shows that SS behavior has fully recovered from p-CPA induced suppression when 5-HT levels are still maximally depleted. The data reveal that the effects of electrical brain SS on p-CPA induced reductions of 5-HT cannot explain the temporal dissociation between 5-HT depletion and SS suppression. As a whole the data suggest that midbrain 5-HT neurons are not critically involved in SS behavior.
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PMID:Time course analysis of para-chlorophenylalanine induced suppression of self-stimulation behavior. 621 66

The effect of ethanol (4 g/kg) as well as the role of serotoninergic neurons on the rate of ovulation and plasma LH, FSH and prolactin secretion have been studied in rats at preovulatory periods (18th hour of diestrus). It has been found that administration of ethanol in preovulatory periods decreased the number of ovules per rat (p less than 0.001), the number of ovulating rats and LH levels (p less than 0.001). These effects were accompanied by an increase in prolactin concentration (0.05 greater than p greater than 0.02), which was followed by a diffuse luteinization in the ovarian tissue. These results showed that ethanol had an effect of central depression in preovulatory periods. These effects could be mediated through the hypothalamic releasing factors. Under previous serotonin depletion with p-chlorophenylalanine (PCPA: 300 mg/kg), ethanol caused similar effects on LH and FSH levels as compared with the control group with PCPA. However, prolactin concentration was not increased. These results showed that serotoninergic neurons could be mediated in changes caused by ethanol on prolactin secretion, but do not affect directly in changes caused on LH and FSH secretion.
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PMID:[Effect of ethanol in preovulatory periods on LH, FSH, prolactin and ovulation in rats]. 622 48

The effects of a single injection of parachlorophenylalanine (PCPA, 300 mg/kg i.p.) on sleep, motor activity and consummatory behavior were investigated in unrestrained rats which were continuously recorded with telemetric techniques on two control days and six drug days. Slow wave sleep (SWS) was defined as the non-REM sleep (NREMS) fraction with a low predominant EEG frequency. In the 24 h following PCPA administration, motor activity and food intake were reduced and sleep was increased. SWS was massively enhanced, while REM sleep (REMS) was depressed. The initial phase of sedation was followed by a phase of partial insomnia lasting 1-2 days. SWS and REMS were particularly depressed. A rebound phenomenon was observed at the end of recovery period when some of the SWS and REMS values exceeded the control level. The administration of tryptophan (Trp, 150 mg/kg i.p.) 28 h after PCPA pretreatment, causing a significant rise in the brain serotonin (5-HT) concentration, produced a temporary increase in SWS and REMS, and a reduction of motor activity. The experiments show that the depression of SWS and REMS, and the hyperactivity 1-2 days after PCPA administration, are a consequence of the reduced 5-HT level, whereas the involvement of serotonergic mechanisms in the initial sedative phase and in the recovery phase is less clear. The persistence of the daily distribution of sleep and activity, and of the specific pattern of SWS and REMS, indicates that the circadian sleep organization is little affected by 5-HT depletion.
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PMID:Effect of p-chlorophenylalanine and tryptophan on sleep, EEG and motor activity in the rat. 645 88

Acute administration of ethanol lowers plasma levels of luteinizing hormone (LH) in several species. Since ethanol may interact with central serotonergic (5HT) neurons, and since 5HT systems have been found to play a role in modulating LH release, we examined the possible role of central serotonergic neurons in the ethanol-induced depression of LH. Acute PCPA (400 mg/kg, 20 hr before 2.0 g/kg ethanol) was effective in preventing the ethanol-induced depression of LH, suggesting that ethanol activates 5HT systems to lower LH. In support of this, the central 5HT agonist 5-methoxy-N, N-dimethyltryptamine (5MDMT) depressed LH in a dose-dependent manner. However, while the effects of a sub-maximal dose of 5MDMT were blocked by prior administration of methysergide, this 5HT receptor antagonist was unable to prevent the post-ethanol fall in LH. Additionally, because other doses of PCPA (250 mg/kg 20 hr prior to ethanol, and 100 mg/kg P.O. x 3 days before ethanol) produced similar reductions in hypothalamic 5HT but did not block the ethanol effect, and because electrolytic lesions of the median raphe nucleus were also ineffective in preventing the post-ethanol depression of LH, we conclude that activation of serotonergic systems does not play a major role in the ethanol induced depression of LH.
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PMID:Antagonism of ethanol-induced decrease in LH by para-chlorophenylalanine: lack of correlation with altered serotonergic mechanisms. 645 51


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