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

To clarify the interaction between anxiety-like behavior produced by corticotropin-releasing factor (CRF) and the 5-HT system, we investigated the effects of intracerebroventricular (i.c.v.) administration of CRF on an elevated plus-maze performance as indices of anxiety, measuring extracellular levels of 5-HT in the ventral hippocampus using an in vivo brain dialysis method in rats. The time spent in the open arms of the maze and the number of open arm entries were decreased in a dose-dependent manner by the administration of CRF (0.3-1.0 microg/rat). These effects of CRF were prevented by pretreatment with a 5-HT(1A) receptor agonist, 8-OH-DPAT (0.5 mg/kg, s.c.). In biochemical studies, CRF increased 5-HT release about 150-250% above baseline in the ventral hippocampus and this elevation was significantly inhibited by a CRF receptor antagonist, alpha-Helical CRF(9-41) (50 mug/rat), and 5-HT(1A) receptor agonist, 8-OH-DPAT (0.5 mg/kg, s.c.). These results suggested that the anxiety-like effect produced by CRF may have involved increased 5-HT transmission in the ventral hippocampus. Taken with the evidence for hypersecretion of CRF in patients with depression and anxiety-related disorders, our findings lead to the intriguing hypothesis that interaction between CRF and 5-HT, especially in the ventral hippocampus, plays a role in the etiology of affective and anxiety disorders.
 ...
PMID:Hippocampal serotonergic system is involved in anxiety-like behavior induced by corticotropin-releasing factor. 1457 94

Variations in estradiol (E(2)) may influence expression of stress-related anxiety and depression symptoms among women. Effects of E(2) and stress on anxiety and depressive behavior were investigated using an animal model. E(2) was administered subcutaneously (0, 2, 5, 10, 20, 50 mug/rat) to ovariectomized rats 2 days before testing. In experiment 1, open field (anxiety), elevated plus maze (anxiety), or forced swim test (depressive) behavior was evaluated following 20 min of restraint or no such stressor. Rats administered 5 or 10 mug E(2), which produced physiological plasma E(2) concentrations, showed significantly less anxiety and depressive behavior and lower corticosterone levels compared to vehicle, lower, or higher E(2) dosages. Restraint stress prior to behavioral testing attenuated the antianxiety and antidepressive effects of 5 or 10 mug E(2). In experiment 2, effects of adrenalectomy or sham surgery and vehicle or corticosterone replacement in their drinking water on behavior and neuroendocrine measures of rats administered 0, 10, or 50 mug E(2) were examined. E(2), 10 mug, compared to vehicle or 50 mug, reduced anxiety and depressive behavior of sham and adrenalectomized rats administered the low dosage of corticosterone, but not vehicle or the high dosage of corticosterone, suggesting that there may be an optimal level of corticosterone necessary for E(2) to exert these effects. Together, these data suggest that E(2) may have dose-dependent effects on anxiety and depressive behavior of female rodents, which may depend on the tone of the hypothalamic-pituitary-adrenal axis.
 ...
PMID:Antianxiety and antidepressive behavior produced by physiological estradiol regimen may be modulated by hypothalamic-pituitary-adrenal axis activity. 1575 6

In the absence of any specific behavioral assay for cannabinoids or endocannabinoids, a cannabinoid-induced profile in a series of four in vivo assays in mice is most commonly used to assess a specific cannabinoid activity at the behavioral level. Thus, when a given compound produces motor depression in an open field, catalepsy on an elevated ring, analgesia on a hot plate, as well as hypothermia, cannabinoid CB1 receptor activation is assumed, although exceptions are possible. The full cannabinoid profile, however, includes for example ataxia in dogs and discrimination learning in rats. In view of (1) the addictive/reward potential of cannabis and the cannabinoids and (2) the multiple roles of the endocannabinoid physiological control system (EPCS) in behavioral functions, including memory, emotionality, and feeding, a number of behavioral techniques have been used to assess the effects of cannabinoids in these functions. In this chapter we will describe the tetrad of cannabinoid-induced effects as well as a series of behavioral assays used in the behavioral pharmacology of marijuana-cannabinoid research. Since the EPCS plays an important role in the developing organism, methods used in the assessment of physical and behavioral development will also be discussed. The techniques include the tetrad, drug discrimination, self-stimulation and self-administration, conditioned place preference/aversion, the plus-maze, chronic mild stress (CMS), ultrasonic vocalizations, cognitive behaviors, and developmental assessment in mouse (and rat) pups.
 ...
PMID:Behavioral methods in cannabinoid research. 1650 14

Corticotropin-releasing factor (CRF), a 41-amino acid peptide, has been recognized as an important factor mediating stress. Efforts to discover small molecule antagonists of the CRF type-1 receptor (CRF(1)-R) for potentially novel treatment of anxiety and depression started in the early 1990's. Although highly potent in vitro and efficacious in animal models, early reported compounds such as CP-154,526 and NBI-27914 are highly lipophilic and possess high plasma protein and tissue binding, long elimination half life, and toxicity, likely due in part to accumulation in tissues. Recently, several laboratories have reported potent CRF(1)-R antagonists with improved physicochemical properties. Compounds such as DMP696, NBI-30775/R121919 and R278995/CRA0450 possess at least one additional polar group in their structures and are therefore less lipophilic than the earlier compounds, while still maintaining high potency. For example, DMP696 has a K(i) value of 1.7 nM and a cLogP of 3.2, which is similar to CP-154,526 in potency but about 4-log units lower in partition coefficient. Despite its high plasma protein binding (98.5% in rat), DMP696 occupies over 50% of brain CRF(1)-R at a total plasma concentration above 100 nM, which is consistent with the doses that produce anxiolytic effects in the rat defense withdrawal test of anxiety. This article will review small molecule CRF(1)-R antagonists by focusing on their pharmacological and pharmacokinetic properties. In addition, the pharmacology of small molecules binding to the CRF(1) receptor will be discussed. An orally available compound with desirable properties in these categories will have a good chance to be developed into a novel treatment for anxiety and depression which may be devoid of the side effects of existing antidepressant treatments.
 ...
PMID:Recent advances in small molecule antagonists of the corticotropin-releasing factor type-1 receptor-focus on pharmacology and pharmacokinetics. 1671 69

The physiological and functional interaction between neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (alpha-MSH) with reference to anxiety and food intake is well documented. An attempt has been made to study the influence of melanocortin (MC) system on NPY induced antidepressant-like effect in rats using Porsolt's forced swim test as the behavioral paradigm. NPY (0.40-2.10 ng/rat), NPY Y1 and Y5 receptors agonist [Leu(31), Pro(34)]-NPY (0.20-0.60 ng/rat) or selective MC4 receptors antagonist HS014 (0.01-0.07 ng/rat) dose dependently elicited antidepressant-like effect. On the other hand, alpha-MSH (100-400 ng/rat) resulted in high immobility suggestive of depression. Antidepressant-like effect of NPY (1.00-2.10 ng/rat) or [Leu(31), Pro(34)]-NPY (0.40-0.60 ng/rat) was significantly reversed by prior treatment of alpha-MSH (100 ng/rat). While antidepressant action of NPY (0.40-1.00 ng/rat) or [Leu(31), Pro(34)]-NPY (0.20-0.40 ng/rat) was enhanced by concurrent administration of HS014 (0.01 ng/rat), the locomotor activity in all the treatment groups was unaffected. These results suggest the possibility that MC and NPYergic systems may interact and regulate the depression via MC4 and NPY Y1 or Y5 receptors.
 ...
PMID:Alpha-melanocyte stimulating hormone antagonizes antidepressant-like effect of neuropeptide Y in Porsolt's test in rats. 1705 48

To investigate the properties of excitatory connections between layer 4 pyramidal cells and whether these differed between rat and cat, paired intracellular recordings were made with biocytin filling in slices of adult neocortex. These connections were also compared with those from layer 4 spiny cells to layer 3 pyramids and connections between layer 3 pyramids. Connectivity ratios for layer 4 pyramid-pyramid pairs (1:14 cat, 1:18 rat) appeared lower than for the other types of connections studied in parallel, but excitatory postsynaptic potential (EPSP) amplitudes and time course were not significantly different either between species or across types of connection. Layer 4 pyramids targeted postsynaptic basal dendrites in both species, whether the pyramidal target was in layer 4 or layer 3. Within layer 4, relationships between mean EPSP amplitude, numbers of putative contacts, and distance between connected pairs indicated a rapid decline in connectivity strength with distance, equivalent to 3.4 mV and 10 synapses per 100 microm separation, from a maximum of 4 mV and 10 synapses at 0 microm. However, a subset, of burst-firing layer 4 pyramids, appeared to make no connections with other layer 4 spiny cells. Second EPSPs were depressed by 36% in rat and 28% in cat relative to first EPSPs at interspike intervals <15 ms. Subsequent EPSPs in brief trains were further depressed. Depression was predominantly presynaptic in origin. Recovery from depression could not be described adequately by a simple exponential for individual connections; it included peaks and troughs with periodicities of 10-15 ms. Complex relationships between the first 2 interspike intervals and third EPSP amplitude were also apparent in all connections so studied. Large third EPSPs followed specific combinations of first and second interspike intervals so that increasing, or decreasing, one without changing the other resulted in a smaller third EPSP. Finally, the outputs of layer 4 spiny cells to layer 3 exhibited partial recovery from depression during longer high-frequency trains, a property not apparent in the other connections studied.
 ...
PMID:Dynamic properties of excitatory synaptic connections involving layer 4 pyramidal cells in adult rat and cat neocortex. 1711 52

Vasopressin and corticotropin releasing factor (CRF) are both critical regulators of an animal's stress response and have been linked to anxiety and depression. As such, antagonists of the CRF1 and V1b receptor subtypes are being developed as potential treatments for affective disorders. The two most characterized V1b and CRF1 antagonists are SSR149415 and CP-154,526, respectively, and the present studies were designed to compare these two compounds in acute animal models of affective disorders. We employed five anxiety models: Separation-induced pup vocalizations (guinea pig and rat), elevated plus-maze (EPM), conditioned lick suppression (CLS), and marble burying (mouse); as well as three depression models: forced swim test (FST; mouse and rat) and tail suspension test (TST; mouse). SSR149415 (1-30 mg/kg) was active in the vocalization, EPM and CLS models, but inactive in marble burying. CP-154,526 (1-30 mg/kg) was active in vocalization models, but inactive in EPM, CLS, and marble burying. SSR149415 was inactive in all depression models; CP-154,526 was active in rat FST but inactive in mouse models. This work demonstrates the different profiles of V1b and CRF1 receptor antagonists and supports both approaches in the treatment of affective disorders.
 ...
PMID:Comparison of the V1b antagonist, SSR149415, and the CRF1 antagonist, CP-154,526, in rodent models of anxiety and depression. 1729 71

We investigated the involvement of alpha-melanocyte stimulating hormone (alpha-MSH) following acute, chronic and withdrawal treatments of ethanol with reference to depression. The degree of depression was evaluated using Porsolt's forced swim test. While intracerebroventricular (i.c.v.) alpha-MSH (100-400 ng/rat) dose-dependently increased the immobility, opposite response was observed following administration of selective MC4 receptor antagonist HS014 (0.01-0.07 ng/rat, i.c.v.). The anti-immobility effect of acute ethanol (1-2 g/kg), injected via intra-peritoneal route (i.p.), was suppressed by central administration of alpha-MSH (100 ng/rat, i.c.v.), but was enhanced following pretreatment with HS014 (0.01 ng/rat, i.c.v.). Chronic ethanol resulted in increased immobility time, while further augmentation in immobility was noticed following ethanol withdrawal. However, concomitant HS014 (0.01 ng/rat, i.c.v.) treatment prevented tolerance as well as attenuated enhanced immobility in ethanol-withdrawn rats. Acute administration of HS014 (0.01-0.03 ng/rat, i.c.v.), at 24h post-withdrawal time point, also antagonized the ethanol withdrawal immobility in rats. The profile of alpha-MSH-immunoreactivity in the paraventricular (PVN), arcuate (ARC), paraventricular thalamic (PVT), dorsomedial hypothalamic-dorsal (DMNd) and -ventral (DMNv) nuclei, lateral hypothalamus (LH) and central nucleus of amygdala (CeA) was investigated with immunocytochemistry. Acute ethanol significantly reduced the alpha-MSH-immunoreactivity in the cells and fibers of ARC, and fibers in the PVN, DMNd, DMNv and CeA. While chronic ethanol treatment significantly increased the alpha-MSH-immunoreactivity as compared to the pair-fed control group, further augmentation was noticed following 24 h ethanol withdrawal. However, the alpha-MSH-immunoreactive profile in the PVT and LH did not respond. alpha-MSH in discrete areas may play a role in ethanol-induced antidepressant-like response and withdrawal-induced depression.
 ...
PMID:Involvement of alpha-melanocyte stimulating hormone (alpha-MSH) in differential ethanol exposure and withdrawal related depression in rat: neuroanatomical-behavioral correlates. 1849 89

Several combinations of effective treatments have been used in the search for higher response rates or more rapid responses than monotherapy to diminish treatment-resistant depression. One strategy is to combine olanzapine plus antidepressant drugs. In preclinical studies in male rats, olanzapine combined with fluoxetine produce antidepressant-like actions and increase the allopregnanolone levels in the brain. 17-beta estradiol also produces antidepressant-like actions by increasing allopregnanolone levels. However, the effects of combining olanzapine with 17-beta estradiol in the forced swimming test have not been tested before. Thus, systemic injections of vehicle plus olanzapine, or fluoxetine (20.0 mg/kg; 25.0 mg/kg) or 17-beta estradiol (10.0 microg/rat; 20.0 microg/rat) reduced immobility by increasing active behaviors, which were cancelled by finasteride (finasteride was used to block the endogenous production of allopregnanolone by the brain) in ovariectomized rats forced to swim. Subthreshold doses of olanzapine (2.5 mg/kg) combined with subthreshold doses of 17-beta estradiol (5.0 microg/rat) produced antidepressant-like actions, as did the combination subthreshold dose of olanzapine (2.5 mg/kg) plus the subthreshold dose of fluoxetine (15.0 mg/kg). Finasteride cancelled the antidepressant-like actions of the several combinations used. It is concluded that olanzapine alone or combined with fluoxetine or estradiol reduced immobility by increasing swimming. In conclusion, olanzapine produces antidepressant-like actions alone or in combination with estradiol. These antidepressant-like actions of this combination were cancelled by finasteride.
 ...
PMID:Olanzapine plus 17-beta estradiol produce antidepressant-like actions in rats forced to swim. 1958 76

Although physical isolation of rats is known to cause anxiety- and depression-like symptoms, the underlying mechanisms are not fully understood. We have attempted to define the role of endogenous melanocortins (MC) in the manifestation of these symptoms. Weaning rats were socially isolated for 6 weeks and subjected to behavioral paradigms like elevated plus maze (EPM), social interaction, and forced swim test (FST). While socially isolated rats spent less time in social interaction, and showed significantly decreased activity in the open arms of the EPM, the immobility time in FST was significantly increased thus reflecting anxiety- and depression-like phenotypes. Intracerebroventricular injection of HS014 (5 or 10 nmol/rat), selective antagonist of MC4 receptors, attenuated these symptoms. This suggested the involvement of endogenous alpha-melanocyte stimulating hormone (alpha-MSH) in anxiety and depression. With a view to determining the neuroanatomical substrates in which the endogenous alpha-MSH may process the related information, profile of the peptide in paraventricular (PVN), arcuate (ARC), dorsomedial hypothalamic-dorsal (DMNd) and -ventral (DMNv) nuclei, and central nucleus of amygdala (CeA) was investigated with immunohistochemistry. While social isolation significantly reduced alpha-MSH-immunoreactivity profile in all these components, re-socialization of the socially isolated rats, over a period of 72 h, resulted in full recovery of the alpha-MSH-immunoreactivity profile; the symptoms of anxiety- and depression-like behaviors were also fully attenuated. We suggest that alpha-MSH in the PVN, ARC, DMNd, DMNv and CeA, acting via MC4 receptors, are involved in manifestation of affective disorders like anxiety and depression.
 ...
PMID:Involvement of alpha-MSH in the social isolation induced anxiety- and depression-like behaviors in rat. 2008 Jan 15


<< Previous 1 2 3 4 5 6 7 8 Next >>