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)

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

The participation of central monoaminergic systems in the regulation of spontaneous motility in developing chick embryos was tested by systemic administration of several drugs, which affect the different sites of central aminergic systems. Amphetamine (2 mg.kg-1 egg weight) evoked an age-dependent depression of spontaneous motility, which first occurred in a significant fashion on day 13 of incubation. Two thirds of this depression depended upon supraspinal influences. The effect of p-chlorophenylalanine (100 mg.kg-1 e.w.) consisted from day 15 of incubation in a short-lasting depression followed by partial recovery of resting motility. alpha-methyldopa (100 mg.kg-1 e.w.) depressed the spontaneous motility from day 13 of incubation, without any signs of recovery within the first hour after drug administration. The most pronounced depressive effect was evoked by melatonin (25 mg.kg-1 e.w.) even in 11-day-old embryos. Along with the increased depth of depression the recovery of motility declined until full cessation of motility was achieved in 17-day-old embryos. The results were interpreted as constituting further evidence for the involvement of central aminergic systems in the development of supraspinal control over spontaneous motor activity generated by the CNS.
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PMID:Development of spontaneous motility in chick embryos. Further components of aminergic mechanisms. 645 76

A direct infusion of amphetamine into the dorsal raphe nucleus of the rat inhibited the activity of serotonergic neurons in this site. An intravenous injection of 5-methoxy-N,N-dimethyltryptamine, a serotonin autoreceptor agonist, mimicked this effect. The amphetamine-induced depression of firing rate was blocked by a subsequent injection of methiothepin, a putative serotonin autoreceptor antagonist, but not by pretreatment with a-methyl-p-tyrosine which depletes brain catecholamines. Amphetamine infusions into the surrounding periaqueductal gray or brainstem reticular formation failed to change dorsal raphe activity. The results of these studies indicate that endogenous serotonin, which can be released by a direct infusion of amphetamine, suppresses neuronal activity in the dorsal raphe nucleus by a process of self-inhibition.
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PMID:Dorsal raphe neurons: self-inhibition by an amphetamine-induced release of endogenous serotonin. 713 34

A cell culture system has been used to examine the effect of various pharmacologic agents on DNA synthesis with the hope of utilizing this system for the evaluation of drugs at the cellular level. Glucocorticoids have been shown to have a differential effect on growth dependent on the cell type studied. For this reason steroidal anti-inflammatory agents were chosen to study in our culture system. Aspirin, a non-steroidal anti-inflammatory agent, was also studied for a comparison with glucocorticoids. The CNS stimulants, caffeine and amphetamines, were studied for their effects on non-target cells in culture and compared with the response of target cells. Doxorubicin, an anti-neoplastic agent, has been shown to depress growth in a variety of cells. This drug was also studied in our culture system. We have found that steroidal anti-inflammatory drugs induced a dose-dependent stimulation of DNA synthesis in normal human fibroblasts that was also age-dependent, while decreasing DNA synthesis in SV40 virus transformed cells. Aspirin (25 micrograms/ml) exhibited a similar response. Human fibroblasts were found to be responsive to the CNS stimulants, exhibiting a dose-dependent decrease in DNA synthesis when exposed to caffeine. Amphetamine (200 microM) depressed DNA synthesis in normal fibroblasts and increased it in SV40 virus transformed cells. All cells studied exhibited a depression of DNA synthesis when treated with doxorubicin (0.1 microgram/ml).
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PMID:Influence of drugs on macromolecular synthesis during cell synchronization. 716 94

Amphetamine and tranylcypromine are structurally related chemical isomers with pharmacologically distinctive activity profiles. Since they are equimolar and structurally similar they may be used to assess the pharmacologically distinctive activity profiles. Since they are equimolar and structurally similar they may be used to assess the pharmacological specificity of a proposed animal model of depression. Adult male Sprague-Dawley rats were exposed to a chronic stress regimen or remained undisturbed. They were then acutely stressed with white noise. The monoamine oxidase inhibitor tranylcypromine was effective in restoring otherwise reduced stress elicited open field activity in chronically stressed rats. Amphetamine did not resemble tranylcypromine or other antidepressants, and produced a variety of effects at least some of which indicated a potential increase rather than reduction in depression consequent to chronic administration.
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PMID:Amphetamine and tranylcypromine in an animal model of depression: pharmacological specificity of the reversal effect. 719 56

Administration of clonidine, 0.05 mg/kg i.p. to mice 30 min before trial significantly depressed the exploration of a Y-maze. This effect was completely antagonized by 1-amphetamine, 0.75 mg/kg i.p., given 10 min before trial, which by itself did not change the behaviour studied. The clonidine-induced behavioural depression also appeared reduced after pretreatment with desipramine (10 mg/kg i.p., 30 min before clonidine) which, like l-amphetamine, by itself was inactive. The above treatment with clonidine significantly reduced the accumulation of dopa after inhibition of central aromatic L-amino acid decarboxylase both in the noradrenaline (NA) rich neocortex and the dopamine-rich neocortex and the dopamine-rich corpus striatum, whereas the dopa accumulation in the limbic brain regions was not significantly affected. l-Amphetamine, 0.75 mg/kg i.p., did not by itself significantly affect the dopa accumulation, but reduced the clonidine-induced effects. The results are compatible with the notion that the depression of exploratory behaviour by clonidine is related to impaired central NA-neurotransmission and rule out the possibility that it is due to activation of central post-synaptic NA-(alpha-)-receptors.
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PMID:Clonidine: attenuation of sedative action by facilitated central noradrenergic neurotransmission. 735 21

Intracranial self-stimulation was assessed before, within, and after a chronic amphetamine treatment regimen. Amphetamine was given twice daily 5 days per week for 6 weeks at dosages escalating from 1 to 10 mg/kg per injection. Lateral hypothalamic self-stimulation rate-frequency functions were taken 36 h after the last injection in each weekly series and weekly for 3 weeks following the last injection. Frequency thresholds increased and maximal response rates decreased progressively as a function of amphetamine withdrawal during treatment; each returned to near normal levels within 2 weeks of the last injection. When subsequently tested under amphetamine, animals previously receiving the 6-week amphetamine treatment regimen had self-stimulation thresholds and maximal response rates that did not differ significantly from those of saline-treated control animals. These data confirm that chronic amphetamine treatment results in a dependence syndrome characterized in part by a phasic depression in the brain mechanism mediating the reinforcing effects of lateral hypothalamic electrical stimulation.
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PMID:Withdrawal from chronic amphetamine elevates baseline intracranial self-stimulation thresholds. 775 58

A sample of drug users (n = 158) were contacted and interviewed in non-clinical community settings about their use of Ecstasy, cocaine powder, and amphetamines and the adverse effects of these drugs. Subjects reported a wide range of adverse effects including anxiety problems, depression, mood swings, feelings of paranoia, and panic attacks. Sleep and appetite disturbances were the most commonly reported problems. About half of all subjects reported depression and paranoid feelings associated with their stimulant use. Many of those reporting problems stated that these were mild. However, for all drugs, a substantial minority of users reported adverse effects which they rated as 'severe'. Between 30 and 55% of the sample reported having had at least one 'severe' adverse effect (30% cocaine, 35% Ecstasy and 55% amphetamine). There were clear differences between the different drugs in the likelihood and reported severity of adverse effects. Amphetamine use was associated with significantly more adverse effects and with more severe adverse effects than Ecstasy or cocaine. Cocaine powder was associated with the least severe adverse effects. A common pattern of drug use involved the use of depressant drugs such as opiates and benzodiazepines in addition to stimulants. The stimulant and depressant users were more likely than the stimulants-only users to use stimulants by injection and more likely to report adverse effects associated with stimulant use. The stimulant and depressant users were also more likely to have been treated for a drug problem. Approximately a quarter of the sample stated that they had stopped using stimulants up to the point of interview as a result of their bad experiences.
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PMID:Adverse effects of stimulant drugs in a community sample of drug users. 908 80

Six men and 3 women on each of 4 days received 10 mg of methylphenidate or placebo (2 times a day) at 0800 and 1200 after 8 hr or 0 hr of sleep. Sleep latency was measured by the Multiple Sleep Latency Test (MSLT) at 0930, 1130, 1330, 1530, and 1730. Participants also completed divided-attention and auditory vigilance tasks at 1000 and 1400 and the Profile of Mood States (POMS) and the Addiction Research Center Inventory (ARCI) after the 0930 and 1330 latency tests. The drug increased mean latency on the MSLT in both sleep conditions. Performance only showed drug effects after prior sleep deprivation. On the POMS, the drug increased Vigor and reduced Fatigue and Depression scale scores, primarily after sleep deprivation. The drug increased the ARCI Amphetamine and Morphine-Benzedrine scores only in the basal state. The ARCI Pentobarbital score was increased by sleep deprivation and decreased by the drug.
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PMID:Alerting effects of methylphenidate under basal and sleep-deprived conditions. 938 61

The United States has experienced three distinct methamphetamine epidemics: one in the 1950s, one in the late 1960s, and the third and current one in the mid-1990s. The current epidemic is closely related to the HIV epidemic. Amphetamine (speed) and methamphetamine use can lead to significant dependence and abuse, impaired judgement, and an increase in sexual risk-taking. Methamphetamine use is most prevalent in the western United States, and the drug is popular in the gay community. There is compelling evidence linking HIV disease and speed use. Some seropositive individuals appear to use amphetamines as self-medication for their HIV-related depression symptoms. Research, outreach, and prevention programs have targeted heroin, cocaine, and crack users, while the growing number of injection drug users who abuse amphetamines has been overlooked. Health care professionals should note each patient's specific drug use history and refer dependent patients to appropriate treatment.
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PMID:Speed use and HIV transmission. 1136 20


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