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

The effects of chronic novel stressors, for 21 days, on the behavior and the serotoninergic (5-HT) system in Sprague-Dawley (SD) and Wistar Kyoto (WKY) rats were studied. Open-field and forced-swim tests revealed a significantly greater behavioral depression in the WKY strain. SD rats showed a decrease in 3H-DPAT binding to 5-HT1A receptors in the hippocampus, whereas WKY rats revealed an increase in 3H-DPAT binding in the hippocampus and hypothalamus. Stress did not appear to alter the binding of 3H-DPAT to 5-HT1A sites in the dorsal raphe or median raphe in either strains. SD rats revealed a modest increase in 5-HT transporter (5-HTT) sites in the cortex; WKY rats revealed a decrease in 5-HTT sites in the cortex and the hippocampus. Stress caused an increase in 3H-CNIMI binding to 5-HTT sites in the dorsal and median raphe nuclei in both strains. The results suggest that the greater susceptibility to behavioral depression in WKY rats may account for the differential effects on 5HT1A sites as well as 5-HTT sites in limbic regions and cell body area as compared to SD rats.
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PMID:Effect of stress on the behavior and 5-HT system in Sprague-Dawley and Wistar Kyoto rat strains. 880 95

Excessive stimulation of serotonin 5HT1A receptors causes a syndrome of serotonin excess that consists of shivering, muscle rigidity, salivation, confusion, agitation and hyperthermia. The most common cause of this syndrome is an interaction between a monoamine oxidase inhibitor (MAOI) and a specific serotonin reuptake inhibitor. Venlafaxine is a new antidepressant agent that inhibits the reuptake of serotonin and norepinephrine. We report a venlafaxine-MAOI interaction that resulted in the serotonin syndrome in a 23-y-old male who was taking tranylcypromine for depression. He had been well until the morning of presentation when he took 1/2 tab of venlafaxine. Within 2 h he became confused with jerking movements of his extremities, tremors and rigidity. He was brought directly to a hospital where he was found to be agitated and confused with shivering, myoclonic jerks, rigidity, salivation and diaphoresis. His pupils were 7 mm and sluggishly reactive to light. Vital signs were: blood pressure 120/67 mm Hg, heart rate 127/min, respiratory rate 28/min, and temperature 97 F. After 180 mg of diazepam i.v. he remained tremulous with muscle rigidity and clenched jaws. He was intubated for airway protection and because of hypoventilation, and was paralyzed to control muscle rigidity. His subsequent course was remarkable for non-immune thrombocytopenia which resolved. The patient's maximal temperature was 101.2 F and his CPK remained < 500 units/L with no other evidence of rhabdomyolysis. His mental status normalized and he was transferred to a psychiatry ward. This patient survived without sequelae due to the aggressive sedation and neuromuscular paralysis.
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PMID:Serotonin syndrome from venlafaxine-tranylcypromine interaction. 888 41

The prefrontal cortex has been reported to be involved in the regulation of emotional behaviour by integrating cognitive, emotional and autonomic information processes, and impairments of its functions are implicated in psychopathologies such as depression. Neuronal functioning in the prefrontal cortex is under the control of the noradrenergic and the serotonergic system which are both activated during stress. The present study aimed to quantify the effect of chronic psychosocial stress on alpha2-adrenoceptors, beta-adrenoceptors, and serotonin1A receptors in the prefrontal cortex. Male tree shrews (Tupaia belangeri) were subjected to subordination stress for 2, 10, 21 and 28 days, and binding sites for the alpha2-adrenergic antagonists 3H-rauwolscine and 3H-RX821002, for the beta-adrenergic antagonist 125I-iodocyanopindolol, and for the 5-hydroxytryptamine (5HT)1A receptor agonist 3H-8-hydroxy-2-(di-n-propylamino)tetralin were quantified by in vitro receptor autoradiography. Chronic psychosocial stress induced time-dependent receptor down- and upregulations. Beta-adrenoceptors were transiently reduced in numbers after just 2 days of psychosocial stress which is interpreted as agonist-mediated downregulation induced by high local concentrations of noradrenaline released from terminals originating from the locus coeruleus. Alpha2-adrenoceptors were transiently downregulated after 10 days, and upregulated after 28 days of psychosocial stress. These data indicate that the noradrenergic system adapts to the stress by counterbalancing its receptor numbers. 5HT1A receptors were only downregulated after 28 days of psychosocial stress, and thus react later than the noradrenergic receptors. In summary, our results show that monoaminergic receptors in the prefrontal cortex of tree shrews undergo dynamic changes during chronic psychosocial stress. These alterations probably have an impact on neuronal activity, and might contribute to the behavioural changes which have been previously described in subordinate male tree shrews.
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PMID:Monoamine receptors in the prefrontal cortex of Tupaia belangeri during chronic psychosocial stress. 904 67

Fluoxetine has been reported to suppress food intake in animal models of feeding. Fluoxetine increases extracellular serotonin in the brain. 5HT1A autoreceptors regulate synaptic levels of serotonin. A combination of a 5HT1A receptor antagonist and fluoxetine has been previously reported to enhance extracellular levels of serotonin over what is obtained with fluoxetine alone. Thus, a combination of fluoxetine and a 5HT1A antagonist could enhance the ability of fluoxetine to suppress appetite. Fluoxetine was tested in a model of feeding, in which CD-1 mice were trained to drink sweetened condensed milk. Fluoxetine was found to attenuate milk drinking, in a dose-dependent manner, at doses greater than 10 mg/kg, i.p. A 10 mg/kg dose of fluoxetine, which was ineffective by itself, was then combined either with 5-hydroxytryptophan (5HTP), a serotonin precursor, or with S(-) pindolol, a 5HT1A/beta adrenergic receptor antagonist or with LY206130, a more selective 5HT1A receptor antagonist. These treatment paradigms resulted in significant attenuation of the consumption of sweetened condensed milk. Since fluoxetine has been shown to be useful in the treatment of eating disorders and to promote weight loss in obese humans, although at doses greater than those required for the treatment of depression, a combination of fluoxetine with a 5HT1A receptor antagonist could be of clinical utility in the treatment of eating disorders and obesity.
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PMID:5HT1A receptor antagonists enhance the functional activity of fluoxetine in a mouse model of feeding. 950 85

Depression, a chronic disease and a leading cause of disability worldwide, will generate increasing needs in terms of public health in the coming years. Many antidepressants are now available. However, these molecules present real limitations and disadvantages. Thus there are great expectations on the part of the clinicians for more efficient drugs that are better tolerated. How can we satisfy such hopes and innovate in this domain today? One original and most promising strategy for developing new antidepressants that are more efficient and better tolerated involves antagonizing both alpha 2-noradrenergic and 5HT2 and 5HT3 serotonergic receptors, without blocking 5HT1A serotonergic receptors. The technology now available in pharmacological research allows the development of such molecules.
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PMID:[Pharmacological management of failure of treatment with antidepressants]. 992 1

The serotonergic system has been implicated in both the aetiology and pharmacological treatment of obsessive compulsive disorder. In pharmacological challenge tests, mCPP, a 5-HT agonist, with an affinity for 5HT2C as well as 5HT1A and 5HT1D receptors, was associated with a transient exacerbation of obsessive compulsive symptoms. Chronic administration of mCPP was found to bring about some relief of these symptoms. Sumatriptan is an antimigraine agent, which interacts most potently with 5HT1D receptors. In the cases to be presented, we report the effects of chronic administration of Sumatriptan to three severe, treatment resistant, OCD patients. Following chronic administration of sumatriptan, these patients, who have been resistant to any former pharmacological treatment, responded with an improvement in their depression and a modest reduction in their obsessive compulsive symptoms.
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PMID:Treatment of severe, drug resistant obsessive compulsive disorder with the 5HT1D agonist sumatriptan. 992 25

Depression, a chronic disease and a leading cause of disability worldwide, will generate increasing needs in terms of public health in the coming years. Many antidepressants are now available. However, these molecules present real limitations and disadvantages. Thus there are great expectations on the part of the clinicians for more efficient drugs that are better tolerated. How can we satisfy such hopes and innovate in this domain today? One original and most promising strategy for developing new antidepressants that are more efficient and better tolerated involves antagonizing both alpha 2-noradrenergic and 5HT2 and 5HT3 serotonergic receptors, without blocking 5HT1A serotonergic receptors. The technology now available in pharmacological research allows the development of such molecules.
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PMID:[Pharmacological approach to failures of antidepressant treatment]. 994 41

Serotonin selective reuptake inhibitors (SSRIs) are currently among the most frequently prescribed therapeutic agents in all of medicine. Their therapeutic actions are diverse, ranging from efficacy in depression to obsessive-compulsive disorder, panic disorder, bulimia and other conditions as well. The plethora of biological substrates, receptors and pathways for serotonin are candidates to mediate not only the therapeutic actions of SSRIs, but also their side effects. Specifically, the immediate actions of SSRIs are mostly side effects, and may be mediated by the initiating actions of SSRIs, namely negative allosteric modulation of the serotonin transporter. A leading hypothesis to explain these immediate side effects is that serotonin is increased at specific serotonin receptor subtypes in discrete regions of the body where the relevant physiologic processes are regulated. Desensitization of post-synaptic receptors in these same discrete brain regions may explain the development of tolerance to these same side effects. The explanation for therapeutic effects characteristic of SSRIs may be found in delayed neurochemical adaptations. A leading hypothesis for this action is desensitization of somatodendritic serotonin 1A autoreceptors in the midbrain raphe. The hypothesis to explain why SSRIs have such diverse therapeutic actions is that somatodendritic 5HT1A autoreceptor desensitization increases serotonin in those critical brain regions and at those key serotonin receptor subtype(s) which may mediate the pathophysiologies of the various disorders. Understanding the topography of serotonin receptor subtypes in discrete anatomical pathways may enhance our understanding of both the therapeutic actions and side effects of these important pharmaceutical agents.
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PMID:Mechanism of action of serotonin selective reuptake inhibitors. Serotonin receptors and pathways mediate therapeutic effects and side effects. 1033 79

Abnormal timing in the circadian system is reported in endogenous depression. Gepirone, a 5HT1A receptor partial agonist, has anxiolytic and antidepressant properties. We determined whether gepirone was able to modify the functioning of the circadian system. Single i.p. injections of gepirone in hamsters induced phase-advances in the circadian activity rhythm when administered during the subjective day, but had no effect when given during the subjective night. Single i.p. gepirone injections also blocked the phase-shifting effects of a light pulse, at a time when gepirone by itself had no effect on the activity rhythm. Chronic gepirone treatment in hamsters kept under a 14/10 light-dark cycle induced a phase-advance in the activity rhythm, modifying the phase-relationship between this rhythm and the light-dark cycle. After transfer to constant darkness, gepirone-treated hamsters showed a shortened free-running period of activity, compared to controls. Both acute and chronic gepirone treatment thus have major effects on the circadian rhythm of locomotor activity in rodents. In view of the hypothesized role for disturbed circadian rhythms in the pathophysiology of depression, and the use of 5HT-related drugs for its treatment, the results provide further support for the possibility that some of the therapeutic effects of these compounds may be due to their effects on temporal organization.
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PMID:Chronobiotic effects of gepirone, a potential antidepressant with 5HT1A receptor partial agonist properties. 1078 Aug 25

The serotonergic system is involved in both pathophysiology and treatment of mood disorders. In the present study we investigated the possible influence of the polymorphisms of the serotonin-1A and 2C receptor genes on the symptomatology of mood disorders. Eighty-four inpatients affected by mood disorders (72 bipolar and 12 major depressive disorder) were assessed by the Operational Criteria Checklist for Psychotic Illness to score their lifetime psychotic symptomatology. The subjects were also typed for 5HT1A and 5HT2C variants using polymerase chain reaction techniques. No association was found between 5HT2C and psychopathology as defined by the four symptomatologic factors used as phenotype definition (mania, depression, delusion, and disorganization) even when bipolar subjects were analyzed separately. Only one subject with the 5HT1A variant was observed. Genetic variation at the 5HT1A and 5HT2C receptor genes does not, therefore, play a major role in the pathogenesis of mood disorders symptomatology. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:161-166, 2000.
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PMID:Serotonin-2C and serotonin-1A receptor genes are not associated with psychotic symptomatology of mood disorders. 1089 89


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