UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropharmacological mechanisms in central regulation of respiration in anesthetized rats were studied in a whole body plethysmographic model. Neurotransmitter agonists and antagonists were administered intracerebroventricularly or locally into the brain and the respiratory pattern was analysed. The four anesthetics: enflurance (E), halothane (H), pentobarbital sodium (P) and urethane (U) were found to have different effects on central respiratory regulation. Respiratory frequency was higher after H and U compared to after E and P. Animals anesthetized with H exhibited a lower inspiratory drive and a slightly depressed sensitivity to CO2. The responses to the neuropeptides substance P and TRH as well as the amino acid neurotransmitter GABA were partly modified after the different forms of anesthesia. Apomorphine (i.c.v) induced a biphasic, haloperidol reversible, respiratory response in H- and U- (but not in E- and P-) anesthetized rats. The initial bradypnoic response might be due to a decreased sensitivity to afferent vagal signals, while the following tachypnoic phase might be elicited by dopaminergic mechanisms at posterior diencephalic and upper midbrain levels (hypoxic, hypercapnic tachypnea). The tachypnoic response was inhibited by a graded exposure to CO2. The effects of different neurotransmitters were further analysed in H-anesthetized animals. GABA and the GABA agonist muscimol exerted a depressant effect on ventilation in contrast to the GABA-like drugs GHBA an baclofen. Exogenous GABA depressed all respiratory parameters studied exept for inspiratory time and was found to affect mainly respiratory timing mechanisms. An increase in endogenous GABA levels induced by the GABA transaminase inhibitor AOAA blunted the respiratory response to CO2 and induced a ventilatory depression similar to that seen after exogenous GABA. A significance correlation between brain stem GABA levels and respiratory duty cycle was found. The tripeptide TRH induced a marked tachypnea due to the extrahypothalamic actions of the peptide. A delay in the response was seen after local injection into the nucleus tractus solitarius and the tachypnea was abolished by CO2 exposure. The ventilatory effects might be elicited by mechanisms similar to those involved in the tachypnoic response to apomorphine. The tachypnea was potentiated by GABA (possibly due to that both agents act on inspiratory off-switch lowering mechanism) and by methylatropine or naloxone (possibly due to secondary pertubation by cholinergic or enkephalinergic mechanisms). A stimulation of ventilation (increase in tidal volume) was seen after substance P (SP) due to an increase in inspiratory drive and o
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PMID:Neuropharmacological aspects of central respiratory regulation. An experimental study in the rat. 620 94

Unilateral motor cortex injury in the cat results in a prolonged loss of tactile placing in the forelimb contralateral to the injury. Amphetamine (5 mg/kg) temporarily reverses this tactile placing deficit as early as 4 days following the injury. Racemic amphetamine was found to produce a significantly more prolonged restoration of placing than the d isomer, which was significantly more effective than the l isomer. Haloperidol (0.4 mg/kg) blocked the amphetamine-induced recovery of placing responses and also blocked placing in nondrugged cats showing partial spontaneous recovery. This dosage of haloperidol had no effect on tactile placing in normal cats. Apomorphine at moderate dosages (0.25 and 0.5 mg/kg) produced a weak restoration of tactile placing in motor cortex-injured animals. These pharmacological data suggest that the loss of tactile placing after motor cortex injury is due to a depression of catecholaminergic function, which is temporarily reversible by catecholaminergic stimulation.
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PMID:Amphetamine and apomorphine restore tactile placing after motor cortex injury in the cat. 640 67

Two lines of mice selectively bred for differences in response to a hypnotic dose of ethanol were administered apomorphine alone or in combination with ethanol. When administered by itself, apomorphine produced similar dose-dependent depression of locomotor activity and increases in stereotypy in the two lines. Doses of apomorphine (0.5 microM/kg and 2 microM/kg) thought to bind only presynaptic dopamine receptors blocked the slight locomotor activation to 1.5 g/kg ethanol in the ethanol-sensitive Long-Sleep (LS) mice; in the ethanol-insensitive Short-Sleep (SS) mice which show marked activation to all subhypnotic doses of ethanol, these doses of apomorphine only attenuated the activation. A higher apomorphine dose (8 microM/kg) antagonized the locomotor depressant effects of 2.0 and 2.5 g/kg of ethanol in LS mice but did not alter the shape of the SS ethanol dose response curve for locomotor activity. Apomorphine (2 and 8 microM/kg) potentiated ethanol-induced loss of the righting reflex in LS mice in a dose dependent fashion, but did not alter this soporific effect of ethanol in SS mice. These findings extend the data base suggesting a role for dopamine both in the mechanism(s) differentiating the LS and SS mice and the stimulant and intoxicating properties of ethanol.
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PMID:Apomorphine effects on behavioral response to ethanol in mice selectively bred for differential sensitivity to ethanol. 653 46

The cardiovascular effects of GABA, sodium valproate (VPA) and inhibitors of GABA-aminotransferase (GABA-T), namely aminooxyacetic acid, gabaculine, gamma-acetylenic GABA, gamma-vinyl GABA and ethanolamine-O-sulphate (EOS), were studied in anesthetized rats, cats and dogs. All compounds were administered intravenously in dose levels previously shown as anticonvulsant active. In rats and cats, GABA (100-1000 mg/kg) caused a sustained fall of blood pressure and heart rate. A similar reaction was observed in dogs following maintenance infusion of the amino acid. The prolonged cardiovascular depression in response to GABA could be attenuated by subsequent administration of picrotoxin and bicuculline as well as by alpha-methyltyrosine, corynanthine, chlorpromazine and tripelennamine. Phentolamine, yohimbine, propranolol, vagotomy, atropine, cyproheptadine, apomorphine and haloperidol did not antagonize the cardiovascular effects of GABA. Administration of GABA-T inhibitors provoked prolonged hypotension and bradycardia, which could be partially counteracted by picrotoxin, bicuculline and, except in the case of EOS, by chlorpromazine. VPA, in high doses (300-400 mg/kg) exerted similar cardiovascular effects in rats as observed with GABA and GABA-T inhibitors. The prolonged cardiovascular depression caused by VPA could be counteracted by bicuculline and partially by chlorpromazine. Apomorphine led to a considerable potentiation of the effects of VPA. It is concluded that GABA, GABA-T inhibitors and VPA may induce cardiovascular depression at least in part by activation of GABA receptors and that the response is mediated predominantly by the central adrenergic system. Some indication was found that an interaction with peripheral histamine contributes to the cardiovascular effects of GABA.
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PMID:Cardiovascular effects of GABA, GABA-aminotransferase inhibitors and valproic acid following systemic administration in rats, cats and dogs: pharmacological approach to localize the site of action. 681 Jul 79

The role of dopamine in spinal motor transmission was investigated using spinal reflexes in acutely spinalized rats. Intravenous administration of a relatively high dose of the dopamine receptor agonist apomorphine-HCl (3 mg/kg) or the D2 receptor agonist bromocriptine mesylate (1 mg/kg) reduced the amplitude of the monosynaptic reflex (MSR). Depression of the MSR by both drugs was antagonized by haloperidol (1 mg/kg), but not by the D2 receptor antagonists YM-09151-2 (0.2 mg/kg) and sulpiride (10 mg/kg), or by a combination of the D1 receptor antagonist SKF 83566 (0.01 mg/kg) and sulpiride (10 mg/kg). Intravenous administration of the selective D1 receptor agonist SKF 77434 (0.1 and 1 mg/kg) and the D2/D3 receptor agonist quinpirole-HCl (0.1 and 1 mg/kg) had no significant effect on the MSR. Simultaneous administration of SKF 77434 and quinpirole had no significant effect on the MSR. These results show that stimulation of D1/D2 receptors has little influence on the MSR, and suggest that descending dopaminergic systems mediating these receptors have little influence on MSR transmission. Apomorphine and bromocriptine may inhibit the MSR via other subtypes of D1/D2 or other, as yet undiscovered, dopamine receptors or via non-dopaminergic mechanisms.
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PMID:Depression of the monosynaptic reflex by apomorphine or bromocriptine is not mediated by D1/D2 receptors. 810 10

We studied the effect of intravenous administration of a dopamine (DA) agonist and antagonist on the hypoxic response of phrenic nerve activity in anesthetized, vagotomized and mechanically ventilated rabbits. The experiments were performed in both intact and carotid sinus denervated animals. In the intact animals, hypoxic challenge (FIO2 = 0.10) increased the amplitude of integrated phrenic nerve activity (iPNA) without any alteration in respiratory frequency. In the carotid sinus denervated animals, the hypoxia progressively depressed iPNA. Neither the DA antagonist, haloperidol (0.5mg/kg i.v.), nor the DA agonist, apomorphine (0.3mg/kg, i.v.) changed the iPNA during normoxia in either the intact or denervated group. Administration of haloperidol enhanced iPNA response to hypoxia in the intact group. Apomorphine decreased the hypoxic response to iPNA. Although apomorphine did not change the control hypoxic response to iPNA in the denervated group, haloperidol augmented hypoxic respiratory depression in the carotid sinus denervated group. Therefore, we concluded that the effect of DA on peripheral chemoreceptors inhibits the hypoxic ventilatory response, but stimulates the hypoxic ventilatory response in the central nervous system.
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PMID:[Effect of dopamine receptor on hypoxic ventilatory response]. 956 75

Immediate behavioral and biochemical effects of single doses of 1,2,3,4-tetrahydroisoquinoline (TIQ, 50 mg/kg) and salsolinol (100 mg/kg), suspected of involvement in etiology of Parkinson's disease, were investigated. Apomorphine (0.25 mg/kg) or haloperidol (1 mg/kg) were administered to TIQ or salsolinol pretreated Wistar rats. In additional experiment the displacement of [3H]apomorphine by TIQ, salsolinol and dopamine receptor agonists and antagonists was tested. Both tetrahydroisoquinolines only slightly affected behavior and dopamine metabolism in naive rats, but very effectively abolished the behavioral and biochemical effects of apomorphine (hyperactivity, depression of striatal HVA level). The behavioral and biochemical effects of haloperidol were unchanged by administration of TIQ nor salsolinol. The tetrahydroisoquinolines displaced [3H]apomorphine from its binding sites with effectiveness comparable to that of dopamine. The results support the hypothesis that endogenous tetrahydroisoquinolines may play an important role in regulation of dopaminergic activity in non-senescent organisms.
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PMID:Antidopaminergic effects of 1,2,3,4-tetrahydroisoquinoline and salsolinol. 1104 Dec 79

Previous studies showed that bladder hyperactivity after cerebral infarction in Sprague-Dawley (SD) rats was mediated in part by D2 dopaminergic and NMDA glutamatergic mechanisms. In the present experiments, the interaction between dopaminergic and glutamatergic excitatory mechanisms in the control of bladder and external urethral sphincter (EUS) reflexes was investigated in urethane-anesthetized sham-operated (SO) and cerebral-infarcted (CI) SD rats. Occlusion of the left middle cerebral artery or a sham operation was performed under halothane anesthesia. Two hours after either of the two procedures, rats were anesthetized with urethane. Dizocilpine, an N-methyl-d-aspartate (NMDA) glutamatergic antagonist, was administered intravenously in doses of 0.3 or 3 mg/kg to CI rats and 3 mg/kg to SO rats. These doses completely inhibited bladder and EUS activity. The effects of apomorphine (a dopamine agonist with greater efficacy at D2 than D1 receptors) or quinpirole (a selective D2 dopamine receptor agonist) were examined on the dizocilpine-induced depression of bladder contractions and EUS EMG activity. Apomorphine did not antagonize the dizocilpine depression of EUS activity, but it did reestablish the micturition reflex after dizocilpine blockade and did increase the amplitude of bladder contractions and voided volume in a dose-dependent manner (0.0001-10 mg/kg, iv), in both CI rats and SO rats pretreated with dizocilpine. There were no differences between SO rats and CI rats in the apomorphine responses in rats pretreated with doses of 0.3 or 3 mg/kg dizocilpine. A larger dose of dizocilpine (10 mg/kg) did not affect the bladder contractions after apomorphine administration. Quinpirole (0.001-1 mg/kg, iv) also partially reversed the dizocilpine depression of bladder activity in SO and CI rats. These results indicate that NMDA glutamatergic and D2 dopaminergic mechanisms exert independent excitatory influences on bladder activity in both SO and CI rats. D2 dopamine receptor agonists can reverse the effect of NMDA receptor blockade on bladder activity but were ineffective in reversing the block of sphincter activity.
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PMID:Interaction between D2 dopaminergic and glutamatergic excitatory influences on lower urinary tract function in normal and cerebral-infarcted rats. 1131 67

A patient in stage 3-4 of the Unified Parkinson's Disease Rating Scale (UPDRS), or in stage 4-5 of Hoehn and Yahr staging scale, or a patient with 0-50% activities of daily living scale of Schwab and England is considered a Late Parkinson's Disease (LPD) patient. The prevalence of disturbed sleep in Parkinson's Disease (PD) was found to vary according to an objective rating, from 60 to 98%. The factors predicting the quality of life in PD patients are: depression, sleep disturbances and dependence. The present article proposes the insertion of the following items as a chapter in a revised UPDRS based on updated knowledge in sleep arousal disturbances in PD. V. SLEEP-AROUSAL DISTURBANCES: Sleep disturbances 43. Light fragment sleep (LFS) 44. Sleep-related breathing disorders (SRBD) 45. Restless legs-periodic leg movements during sleep (RLS-PLM) 46. REM behavioral disorders (RBD) 47. Sleep-related hallucinations (SRH) 48. Sleep-related psychotic behavior (SRPB) Arousal disturbances 49. Sleep attacks (SA) 50. Excessive daytime sleepiness (EDS). Approaching the treatment of disturbed sleep in LPD means postponement of the institutionalization of the LPD patient, allowing the spouse or the caregiver a quiet nights sleep. This approach consists of three steps, each one of major importance. (1) Correct diagnosis based on detailed anamnesis of the patient, of the spouse or of the caregiver; a one week recording on a symptom diary (log) by the patient or the caregiver; excluding co morbidities. Then choosing the most appropriate sleep test, if necessary: polysomnography (PSG), multiple sleep latency test (MSLT), multiple wake latency test (MWLT), actigraphy or video-PSG. This first step allows the diagnosis of one of the above mentioned sleep-arousal disturbances. (2) The non-specific therapeutic approach consists of: (a) checking the sleep effect on motor performance: beneficial, worse or neutral. (b) Dopaminergic adjustment is necessary due to the progression of the nigrostriatal degeneration and the increased sensitivity of the terminals which alter the normal modulator mechanisms of motor centers in LPD patients. Among the many neurotransmitters of the nigro-striatal pathway one can distinguish two with a major influence on REM and non-REM sleep. REM sleep corresponds to an increased cholinergic receptor activity and a decreased dopaminergic activity. This is the reason why REM sleep deprivation by suppressing cholinergic receptor activity ameliorates LPD motor symptoms. L-Dopa and its agonists by suppressing cholinergic receptors suppress REM sleep. L-Dopa has also an arousal effect on Non-REM sleep, repeatedly awakening the patient and enhancing the fragmentation due to the involuntary movements. (c) Socio-physical assistance. (3) The specific therapy consists of: LFS-Sinemet CR, Tolcapone, Intranasal Desmopressin, Domperidon, Cisapride and neurosurgery; SRBD-CPAP, UPPP, nasal interventions, losing weight; RLS-PLM-Benzodiazepine (Clonazepam), Opioid, Apomorphine infusion; RBD-Clonazepam and dopaminergic agonists; SRH-Clozapine, Risperidone; SRPD-Nortriptyline, Clozapine, Olanzepine; SA-adjustment; EDS-arousing drugs. Each therapeutic approach must be tailored to the individual LPD patient.
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PMID:Approaching disturbed sleep in late Parkinson's Disease: first step toward a proposal for a revised UPDRS. 1148 77

The present article is meant to suggest an approach to the guidelines for the therapy of sleep disturbances in Parkinson's Disease (PD) patients.The factors affecting the quality of life in PD patients are depression, sleep disturbances and dependence. A large review of the literature on sleep disturbances in PD patients, provided the basis for the following classification of the sleep-arousal disturbances in PD patients. We suggest a model based on 3 steps in the treatment of sleep disturbances in PD patients. This model allowing the patient, the spouse or the caregiver a quiet sleep at night, may postpone the retirement and the institutionalization of the PD patient. I. Correct diagnosis of sleep disorders based on detailed anamnesis of the patient and of the spouse or of the caregiver. One week recording on a symptom diary (log) by the patient or the caregiver. Correct diagnosis of sleep disorders co morbidities. Selection of the most appropriate sleep test among: polysomnography (PSG), multiple sleep latency test (MSLT), multiple wake latency test (MWLT), Epworth Sleepiness Scale, actigraphy or video-PSG. II. The nonspecific therapeutic approach consists in: a) Checking the sleep effect on motor performance, is it beneficial, worse or neutral. b) Psycho-physical assistance. c) Dopaminergic adjustment is necessary owing to the progression of the nigrostriatal degeneration and the increased sensitivity of the terminals, which alter the normal modulator mechanisms of the motor centers in PD patients. Among the many neurotransmitters of the nigro-striatal pathway one can distinguish two with a major influence on REM and NonREM sleep. REM sleep corresponds to an increased cholinergic receptor activity and a decreased dopaminergic activity. This is the reason why REM sleep deprivation by suppressing cholinergic receptor activity ameliorates PD motor symptoms. L-Dopa and its agonists by suppressing cholinergic receptors suppress REM sleep. The permanent adjustment according to the progression of the degenerative process of the disease will diminishe aggravation. The following types of sleep-arousal disturbances have to be considered in PD patients: - Sleep Disturbances, Light Fragmented Sleep (LFS), Abnormal Motor Activity During Sleep (AMADS), REM Behavior Disorders (RBD), Sleep Related Breathing Disorders (SRBD), Sleep Related Hallucinations (SRH), Sleep Related Psychotic Behavior (SRPB). - Arousal Disturbances, Sleep Attacks (SA), Excessive Daytime Sleepiness (EDS), Each syndrome has to receive a score according to its severity. III. The specific therapy consists in: LFS: Benzodiazepines & Nondiazepines. AMADS: Clonazepam, Opioid, Apomorphine infusion; RBD: Clonazepam and dopaminergic agonists; SRBD: CPAP, UPPP, nasal interventions, losing weight; SRH: Clozapine, Risperidone; SRPD: Nortriptyline, Clozapine, Olanzepine; SA-adjustment; EDS-arousing drugs. Each therapeutic approach must be tailored to the individual PD patient.
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PMID:Sleep disturbances in Parkinsonism. 1258 74

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