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)

Many symptoms of human depressive disorders are also observed in animals after exposure to unpredictable stressors. The chronic mild stress (CMS) paradigm was developed in order to better model the human situation by using chronic mild stressors over a longer period. It is claimed that the model induces anhedonia in the animals, a core symptom of depression in humans. Despite the fact that the CMS model has a high degree of face validity, there are a number of laboratories in which the establishment of the model is less reliably observed. We have examined behavior (sexual activity and open field activity) together with hedonic measures (sucrose and saccharine intake) after exposure to CMS. CMS decreased male sexual activity (e.g. reduced capability to ejaculate) and increased activity in an open field test. The hedonic measures showed diverging results after CMS in our laboratory. Sucrose consumption was reduced, while saccharine consumption did not show a comparable change. It is concluded that CMS induces comparable alterations to some depression-like symptoms in humans. Saccharine consumption is not a reliable indicator of the hedonic responsiveness to CMS.
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PMID:Effects of chronic mild stress on sexual behavior, locomotor activity and consumption of sucrose and saccharine solutions. 1581 92

Sugar beet and sugar cane molasses have been shown to be suitable starting materials for producing de-icer preparations. The sucrose in the molasses is hydrolyzed to glucose and fructose by invertase. The reducing sugars are then degraded by NaOH, the alkali being neutralized by the sugar acids produced, resulting in an increase of the ionic strength and consequently depression of the freezing point of the resulting solution. For the preparation of de-icers, the desired freezing point depression to a temperature of less than about -20 degrees C can be achieved by adjusting the amount and concentration of the alkali metal hydroxide used. The resulting products are biodegradable and eliminate the corrosive effects associated with the use of conventional chloride salts. Degradation of invert sugar by NaOH has been achieved without an external heat source. The reaction products showed the same freezing point depression as seen in the degradation products from pure glucose.
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PMID:Alkaline degradation of invert sugar from molasses. 1722 51

The explanation for the increased prevalence of neuropsychiatric disorders in epilepsy patients is uncertain, with both biological and psychosocial factors proposed. Increasing evidence supports the idea of shared neurobiological processes leading both to seizures and to behavioral, emotional and cognitive disturbance. This study addresses this using Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a model of human generalized epilepsy. We subjected GAERS (n=47) and Non-Epileptic Control rats (NEC; n=73) to behavioral measures of depression and anxiety at 7 and 13 weeks of age, ages prior to and after seizure onset. We employed the Sucrose-Preference Test (SPT), the Elevated Plus Maze (EPM), and the Open Field Arena (OFA). GAERS exhibited significantly greater levels of both depression- and anxiety-like behaviors on all measures, including reduced consumption of sucrose solution in the SPT; lower percentage of time in the open arms of the EPM; and reduced exploratory activity and less time spent in the inner area of the OFA. These differences were evident at both 7 and 13 weeks of age, before and after the onset of epilepsy. Increased anxiety- and depressive-like behaviors are observed in GAERS. These behavioral differences exist before the onset of seizures indicating that they are not secondary consequences of seizures, and suggest shared factors in the biological diathesis underlying the two kinds of disorder. Studying affective disturbance in animal models of epilepsy may illuminate the pathogenesis of affective disorder more generally, as well as modeling psychiatric comorbidities common in epilepsy patients.
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PMID:Elevated anxiety and depressive-like behavior in a rat model of genetic generalized epilepsy suggesting common causation. 1802 21

A 3-week chronic mild stress (CMS) protocol decreased sucrose preference of rats and increased immobility in the forced swim test. It also induced social avoidance and increased grooming, but acted as if reducing anxiety in the plus-maze. Sucrose preference and social avoidance, but not other measures of the behaviour, showed significant correlation. We conclude that CMS-induced depression-like behaviour is associated with social avoidance, a seemingly anxiety-related measure, but not with other anxiety-like traits in rats.
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PMID:Chronic mild stress generates clear depressive but ambiguous anxiety-like behaviour in rats. 1859 Jul 71

Antidepressant drugs produce therapeutic actions and many of their side effects via blockade of the plasma membrane transporters for serotonin (SERT/SLC6A2), norepinephrine (NET/SLC6A1), and dopamine (DAT/SLC6A3). Many antidepressants block several of these transporters; some are more selective. Mouse gene knockouts of these transporters provide interesting models for possible effects of chronic antidepressant treatments. To examine the role of monoamine transporters in models of depression DAT, NET, and SERT knockout (KO) mice and wild-type littermates were studied in the forced swim test (FST), the tail suspension test, and for sucrose consumption. To dissociate general activity from potential antidepressant effects three types of behavior were assessed in the FST: immobility, climbing, and swimming. In confirmation of earlier reports, both DAT KO and NET KO mice exhibited less immobility than wild-type littermates whereas SERT KO mice did not. Effects of DAT deletion were not simply because of hyperactivity, as decreased immobility was observed in DAT+/- mice that were not hyperactive as well as in DAT-/- mice that displayed profound hyperactivity. Climbing was increased, whereas swimming was almost eliminated in DAT-/- mice, and a modest but similar effect was seen in NET KO mice, which showed a modest decrease in locomotor activity. Combined increases in climbing and decreases in immobility are characteristic of FST results in antidepressant animal models, whereas selective effects on swimming are associated with the effects of stimulant drugs. Therefore, an effect on climbing is thought to more specifically reflect antidepressant effects, as has been observed in several other proposed animal models of reduced depressive phenotypes. A similar profile was observed in the tail suspension test, where DAT, NET, and SERT knockouts were all found to reduce immobility, but much greater effects were observed in DAT KO mice. However, to further determine whether these effects of DAT KO in animal models of depression may be because of the confounding effects of hyperactivity, mice were also assessed in a sucrose consumption test. Sucrose consumption was increased in DAT KO mice consistent with reduced anhedonia, and inconsistent with competitive hyperactivity; no increases were observed in SERT KO or NET KO mice. In summary, the effects of DAT KO in animal models of depression are larger than those produced by NET or SERT KO, and unlikely to be simply the result of the confounding effects of locomotor hyperactivity; thus, these data support reevaluation of the role that DAT expression could play in depression and the potential antidepressant effects of DAT blockade.
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PMID:Animal models of depression in dopamine, serotonin, and norepinephrine transporter knockout mice: prominent effects of dopamine transporter deletions. 1869 Jan 11

The "Dopamine Deficiency Hypothesis" and a considerable number of recent pharmacological studies propose to thoroughly verify and improve the standard of knowledge regarding a possible role of dopamine in the pathogenesis and treatment of depression. To elucidate the potential role of D3 receptors in the development of a depressive-like phenotype, we subjected D3 receptor knockout mice to a series of selected behavioural paradigms particularly focussing on depressive-like traits. In our experimental design we exposed animals with a deficiency of the D3 receptor (D3-/-) to a standardised behavioural test battery, in which general changes of locomotion, exploration, anxiety and depressive-like characteristics (i.e. Learned Helplessness, Sucrose Consumption and Forced Swim test) can be detected. Thorough behavioural phenotyping, however, neither revealed behavioural consequences on the basal level (locomotion, exploration) nor depressive- or anxiety-like alterations. Hence, these results do not indicate an evident involvement of the D3 receptor in the development of a depression-like syndrome in mice for now. This does, however, not exclude the D3 receptor as a potential target for pharmacotherapy.
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PMID:Dopamine receptor 3 (D3) knockout mice show regular emotional behaviour. 1883 38

Sugar supplementation can stimulate rumen microbial growth and possibly fiber digestibility; however, excess ruminal carbohydrate availability relative to rumen-degradable protein (RDP) can promote energy spilling by microbes, decrease rumen pH, or depress fiber digestibility. Both RDP supply and rumen pH might be altered by forage source and monensin. Therefore, the objective of this study was to evaluate interactions of a sugar source (molasses) with monensin and 2 forage sources on rumen fermentation, total tract digestibility, and production and fatty acid composition of milk. Seven ruminally cannulated lactating Holstein cows were used in a 5 x 7 incomplete Latin square design with five 28-d periods. Four corn silage diets consisted of 1) control (C), 2) 2.6% molasses (M), 3) 2.6% molasses plus 0.45% urea (MU), or 4) 2.6% molasses plus 0.45% urea plus monensin sodium (Rumensin, at the intermediate dosage from the label, 16 g/909 kg of dry matter; MUR). Three chopped alfalfa hay diets consisted of 1) control (C), 2) 2.6% molasses (M), or 3) 2.6% molasses plus Rumensin (MR). Urea was added to corn silage diets to provide RDP comparable to alfalfa hay diets with no urea. Corn silage C and M diets were balanced to have 16.2% crude protein; and the remaining diets, 17.2% crude protein. Dry matter intake was not affected by treatment, but there was a trend for lower milk production in alfalfa hay diets compared with corn silage diets. Despite increased total volatile fatty acid and acetate concentrations in the rumen, total tract organic matter digestibility was lower for alfalfa hay-fed cows. Rumensin did not affect volatile fatty acid concentrations but decreased milk fat from 3.22 to 2.72% in corn silage diets but less in alfalfa hay diets. Medium-chain milk fatty acids (% of total fat) were lower for alfalfa hay compared with corn silage diets, and short-chain milk fatty acids tended to decrease when Rumensin was added. In whole rumen contents, concentrations of trans-10, cis-12 C(18:2) were increased when cows were fed corn silage diets. Rumensin had no effect on conjugated linoleic acid isomers in either milk or rumen contents but tended to increase the concentration of trans-10 C(18:1) in rumen samples. Molasses with urea increased ruminal NH(3)-N and milk urea N when cows were fed corn silage diets (6.8 vs. 11.3 and 7.6 vs. 12.0 mg/dL for M vs. MU, respectively). Based on ruminal fermentation characteristics and fatty acid isomers in milk, molasses did not appear to promote ruminal acidosis or milk fat depression. However, combinations of Rumensin with corn silage-based diets already containing molasses and with a relatively high nonfiber carbohydrate:forage neutral detergent fiber ratio influenced biohydrogenation characteristics that are indicators of increased risk for milk fat depression.
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PMID:Interaction of molasses and monensin in alfalfa hay- or corn silage-based diets on rumen fermentation, total tract digestibility, and milk production by Holstein cows. 1910 86

Studies have shown that maternal chronic stress or depression is linked to an increased risk for affective disorders in progeny. However, the impact of maternal chronic stress before pregnancy on their progeny in animal models has not been well studied. We investigated the behaviors and the neurobiology in 60-day-old male progeny of maternal rats exposed to a 21-day chronic unpredictable stress (CUS) before pregnancy, with male progeny of unstressed maternal rats as the control. Sucrose consumption test showed that both sucrose intake and sucrose consumption percentage of the CUS progeny were lower than those of the control progeny (P<0.05). The number of times crossing the removed hidden platform in the CUS progeny was significantly fewer than that in the control progeny in Morris water maze test (P<0.05). The level of 5-hydroxytryptamine (5-HT) in the hypothalamus was reduced but the level of norepinephrine (NE) in the hippocampus was increased in CUS progeny when compared to the control (P<0.05). Western blotting showed that the relative level of phosphorylated CREB (P-CREB) in the CUS progeny was lower than that in the control progeny (P<0.05). There were significant positive correlations between sucrose consumption percentage and the level of 5-HT in hypothalamus P<0.05) or the level of P-CREB in hippocampus (P<0.05). In conclusion, depression or stressful events before pregnancy was also associated with high risk of depression in progeny, and the down-regulation of P-CREB in the hippocampus might be one of the mechanisms underlying depression in the CUS progeny.
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PMID:Behavioral and neurobiological studies on the male progeny of maternal rats exposed to chronic unpredictable stress before pregnancy. 2001 28

The prevalence of major depressive disorder (MDD) in adult men is roughly half that of women. Clinical evidence supports a protective effect of androgens against depressive disorders in men. The developing brain is subject to androgen exposure but a potential role for this in depression during adulthood has not been considered. In order to explore this question we treated newborn male rat pups with the androgen receptor antagonist flutamide to block endogenous androgen action and then conducted behavioral tests prior to puberty. Depression-like behaviors were assessed with the Forced Swim Test (FST) and the Sucrose Preference Test (SPT), and anxiety-like behaviors were assessed with the Open Field Test (OFT) and the Novelty-Suppressed Feeding Test (NSFT). Compared to the vehicle-treated controls, neonatal-flutamide treatment caused a significant increase in depression-like behaviors in preadolescent male rats but did not cause any significant difference in anxiety-like behaviors. In separate experiments, male pups with and without flutamide treatment were injected with 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU) from postnatal day (PND) 1 to 4 to label newly produced cells or the hippocampi were Golgi-Cox imbedded and pyramidal neurons visualized. Three lines of evidence indicate neonatal flutamide treatment inhibits hippocampal neurogenesis and neuronal dendritic spine formation in preadolescent male rats. Compared to vehicle controls, flutamide treatment significantly decreased (1) the number of microtubule-associated protein-2+ (MAP-2) neurons in the CA1 region, (2) the number of MAP-2+ neurons in the dentate gyrus (DG) region of the hippocampus, and (3) the density of dendritic spines of pyramidal neurons in the CA1 region. However, there was no effect of flutamide treatment on the number of glial fibrillary acidic protein (GFAP)+ or GFAP+/BrdU+ cells in the hippocampus. This study suggests that the organizational effect of androgen-induced hippocampal neurogenesis is antidepressant.
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PMID:Effects of neonatal flutamide treatment on hippocampal neurogenesis and synaptogenesis correlate with depression-like behaviors in preadolescent male rats. 2039 56

Maltreatment from the caregiver induces vulnerability to later life psychopathologies, yet attraction and comfort is sometimes provided by cues associated with early life maltreatment. We used a rat model of early life maltreatment with odor-0.5 mA shock conditioning to produce depressive-like behaviors and questioned whether stimuli associated with maltreatment would restore emotional neurobehavioral function to control levels. Pups received daily novel odor-0.5 mA shock conditioning from postnatal day 8 to 12. This procedure produces a new maternal odor that controls pups' attachment behaviors. In adulthood, either with or without the infant odor, animals received a Forced Swim Test, Sucrose Preference Test or assessment of amygdala and olfactory system functioning using field potential signal evoked by olfactory bulb paired-pulse electrical stimulation. Following neonatal odor-shock pairings, but not unpaired controls, adults without the odor present showed increased depression-like behavior in the Forced Swim Test and Sucrose Preference Test and a deficit in paired-pulse inhibition in amygdala and piriform (olfactory) cortex. All effects were brought to control levels when the infant conditioned odor was presented during behavioral and neural tests. The ability of cues associated with early life maltreatment to normalize behavior and amygdala activity suggests these cues provide adaptive value in adulthood.
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PMID:Adult depression-like behavior, amygdala and olfactory cortex functions are restored by odor previously paired with shock during infant's sensitive period attachment learning. 2103 82


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