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

1. Changes in respiratory variables, arterial blood pressure and heart rate were studied in awake rats after injection of the opioid peptide [Lys7]dermorphin and its main metabolites, [1-5]dermorphin and [1-4]dermorphin. 2. Fifteen minutes after injection, doses of [Lys7]dermorphin producing antinociception (i.c.v., 36-120 nmol; s.c., 0.12-4.7 micromol kg(-1)) significantly increased respiratory frequency and minute volume of rats breathing air or hypoxic inspirates. This respiratory stimulation was reversed to depression by the 5-HT receptor antagonist ritanserin (2 mg kg(-1), s.c.), was blocked by naloxone (0.1 mg kg(-1), s.c.), significantly reduced by the mu1 opioid receptor antagonist naloxonazine (10 mg kg(-1), s.c., 24 h before) but unaffected by peripherally acting opioid antagonist naloxone methyl bromide (3 mg kg(-1), s.c.). Forty five minutes after injection, doses of the peptide producing catalepsy (s.c., 8.3-14.2 micromol kg(-1), i.c.v., 360 nmol) significantly reduced respiratory frequency and volume of rats breathing air and blocked the hypercapnic ventilator response of rats breathing from 4% to 10% CO2. I.c.v. administration of [1-5]dermorphin and [1-4]dermorphin (from 36 to 360 nmol) never stimulated respiration but significantly reduced basal and CO2-stimulated ventilation. Opioid respiratory depression was only antagonized by naloxone. 3. In awake rats, [Lys7]dermorphin (0.1-1 mg kg(-1), s.c.) decreased blood pressure. This hypotensive response was abolished by naloxone, reduced by naloxone methyl bromide and unaffected by naloxonazine. 4. In conclusion, the present study indicates that analgesic doses of [Lys7]dermorphin stimulate respiration by activating central mu1 opioid receptors and this respiratory stimulation involves a forebrain 5-hydroxytryptaminergic excitatory pathway.
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PMID:Respiratory and cardiovascular effects of the mu-opioid receptor agonist [Lys7]dermorphin in awake rats. 964 52

A technique for thermal imaging of the animal and human brain cortex using an infrared optical system is described. Thermoencephaloscopy (TES) is based on improved thermovision and image processing techniques and allows two-dimensional, contact-free, dynamic and non-invasive recording of background and evoked cortical activity through an unopened skull. Activated (heated) and deactivated (cooled) zones of the cerebral cortex are revealed. The instrumental temporal resolution of TES is 40 msec (25 maps sec-1), the spatial resolution is up to 70 x 70 microns pixel-1. The diameter of the smallest recordable active region of the cortex is 200-300 microns. TES allows to detect the position, size and sequence of activation of precisely located specific cortical zones, and to measure their dynamics before, during and after sensory and direct cortical stimulation, motor acts and conditioning (associative learning). TES effects were recorded in rats, rabbits, cats, monkeys and humans. Waves were found spreading over the cortex with a speed up to 33 mm sec-1 along trajectories specific for the sensory modality and the site of stimulation. Some pathological processes in the brain are detectable by TES: spreading depression; stress; catalepsy; experimental tumors; and epileptic focuses. The main mechanisms of thermal responses recorded by TES are discussed: neural activity; local metabolism of units; local cerebral blood flow; and thermoconductivity in the activated zones of the cortex. Thermoencephaloscopy is a dynamic, non-invasive, contact-free, comparatively cheap, simple and inexpensive method of neuroimaging with a relatively high temporal and spatial resolution and sensitivity. It can be a useful tool in basic neuroscience and medicine.
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PMID:Functional imaging of the brain by infrared radiation (thermoencephaloscopy). 977 Feb 41

Cannabis and cannabinoids exert many of their biological functions through receptor-mediated mechanisms. Two types of cannabinoid receptors have been identified, namely CB(1) and CB(2), both coupled to a G protein. CB(1) receptors have been detected in the central nervous system (where they are responsible for the characteristic effects of Cannabis, including catalepsy, depression of motor activity, analgesia and feelings of relaxation and well being) and in peripheral neurons (where their activation produces a suppression in neurotransmitter release in the heart, bladder, intestine and vas deferens). Cannabinoid CB(2) receptors have only been detected outside the central nervous system, mostly in cells of the immune system, presumably mediating cannabinoid-induced immunosuppression and antinflammatory effects. With the discovery of cannabinoid receptors for exogenous cannabinoids, also endogenous cannabinoids (anandamide, 2-arachidonylglycerol) have been described.
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PMID:Cannabis and cannabinoid receptors. 1093 Jul 7

Although the majority of cannabinoid users smoke marijuana, the preponderance of laboratory animal research is based on administration of Delta9-tetrahydrocannabinol (Delta9-THC) or other cannabinoid agents via injection. The aim of the present study was to evaluate the impact of inhaling marijuana, or ethanol-extracted placebo smoke in the mouse model of cannabinoid activity by assessing inhibition of spontaneous activity, antinociception, catalepsy, and body temperature. In order to determine dosimetry, blood levels of Delta9-THC were obtained following either marijuana exposure or intravenous injection of Delta(9)-THC. Inhalation exposure to marijuana produced dose-related increases in antinociception and catalepsy, with estimated ED50 doses of Delta9-THC of 2.4 and 3.8 mg/kg, respectively. However, hypothermia and locomotor depression occurred in both the placebo- and marijuana-exposed mice. The CB1 receptor antagonist, SR 141716A antagonized the antinociceptive effects of marijuana (AD50 = 0.6 mg/kg), but only slightly decreased marijuana-induced catalepsy, and failed to alter either the hypothermic or locomotor depressive effects. In contrast, SR 141716A antagonized the antinociceptive, cataleptic, and hypothermic effects of intravenously administered Delta9-THC in mice that were exposed to air alone, though all subjects exhibited locomotor depression, possibly related to the restraint. In accordance with reports of others, these data suggest that exposure to smoke alone has pharmacological consequences. Our findings also indicate that marijuana-induced antinociception is mediated through a CB1-receptor mechanism of action and are consistent with the notion that Delta9-THC is mainly responsible for this effect.
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PMID:The pharmacological activity of inhalation exposure to marijuana smoke in mice. 1137 14

Typological behavior reactions of WAG/Rij rats were studied from the standpoint of divergent modulatory integration hypothesis. This rat strain has a genetically determined dominant dysfunction of the benzodiazepine system of the thalamic nuclei. This disorder provokes an epileptiform disease such as absence epilepsy. It was suggested that the dysfunction of this system would result in a modification of the modulatory systems, which support the motivation states of escape and avoidance reactions as well as of the modulatory systems, which form the emotional states. Modifications of these states are the background of typological behavioral features of WAG/Rij rats. It was shown that WAG/Rij have the lower threshold of the development of haloperidol catalepsy, higher levels of fear and depression. On the first day of training in a shuttle box, WAG/Rij rats demonstrated better avoidance performance than Wistar rats. On the second and 28th days, the amnestic effect of the epileptiform disease was observed. The amnestic effect was also observed after passive avoidance conditioning. The results are discussed in terms of the modulatory integratin hypothesis.
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PMID:[Possible mechanisms for forming typological features of behavior of WAG/Rij line rats]. 1187 Oct 35

There is growing scientific, clinical, commercial and regulatory recognition that enantiomers offer benefits over racemates in the management of psychiatric diseases as well as in clinical medicine generally. However, relatively few studies consider enantiomers' individual characteristics. This review considers some of the clinical benefits associated with using stereochemically pure drugs in psychiatric conditions other than depression.A review of the evidence shows that enantiomers offer four main benefits. Firstly, using a single enantiomer may allow a reduction in total dose, while maintaining or improving outcomes. For example, (+)-nefopam's antinociceptive activity is greater than that produced by both the racemate and (-)-nefopam, but with the same level of acute toxicity. Thus, a single enantiomer may offer greater efficacy, dose for dose, than the racemate. Secondly, assessing dose-response relationships is simpler. There is no reason to suppose that a racemate will necessarily contain the isomers' optimum therapeutic ratio, that one of the isomers will be inactive or that the enantiomers' dose-response curves will coincide. For example, the dose-response relationship for the induction of catalepsy in the rat by thioridazine suggested that the racemate was around 12 times more potent than (+)-thioridazine and three times more potent than (-)-thioridazine, when considering the actual concentrations in the striatum. Thirdly, using a single enantiomer may reduce pharmacokinetic and pharmacodynamic variability between patients. For example, the coefficients of variation for some of methadone's pharmacokinetic parameters may reach 70%, which might have clinical consequences. Finally, using a single enantiomer may reduce toxicity arising from the therapeutically inactive stereoisomer. For example, the single enantiomers of bupivacaine and ropivacaine are significantly less cardiotoxic than their respective racemates.This review illustrates why stereochemistry should be considered when assessing the toxicology, pharmacokinetics, metabolism and efficacy of a racemate. Indeed, the differences may be so marked that achiral analyses may be misleading, and clinicians should consider prescribing an enantiomer whenever possible. In many cases, prescribing a single enantiomer improves the benefit:risk ratio. Finally, there is no reason to suppose that a racemate's characteristics will apply to the constituent enantiomers. Copyright 2001 John Wiley & Sons, Ltd.
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PMID:An introduction to enantiomers in psychopharmacology. 1240 12

Dopamine constitutes about 80% of the content of central catecholamines and has a crucial role in the etiology of several neuropsychiatric disorders, including Parkinson's disease, depression and schizophrenia. Several dopaminergic drugs are used to treat these pathologies, but many problems are attributed to these therapies. Within this context, the search for new more efficient dopaminergic agents with less adverse effects represents a vast research field. The aim of the present study was to report the structural design of two N-phenylpiperazine derivatives, compound 4: 1-[1-(4-chlorophenyl)-1H-4-pyrazolylmethyl]-4-phenylhexahydropyrazine and compound 5: 1-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-ylmethyl]-4-phenylhexahydropyrazine, planned to be dopamine ligands, and their dopaminergic action profile. The two compounds were assayed (dose range of 15-40 mg/kg) in three experimental models: 1) blockade of amphetamine (30 mg/kg, ip)-induced stereotypy in rats; 2) the catalepsy test in mice, and 3) apomorphine (1 mg/kg, ip)-induced hypothermia in mice. Both derivatives induced cataleptic behavior (40 mg/kg, ip) and a hypothermic response (30 mg/kg, ip) which was not prevented by haloperidol (0.5 mg/kg, ip). Compound 5 (30 mg/kg, ip) also presented a synergistic hypothermic effect with apomorphine (1 mg/kg, ip). Only compound 4 (30 mg/kg, ip) significantly blocked the amphetamine-induced stereotypy in rats. The N-phenylpiperazine derivatives 4 and 5 seem to have a peculiar profile of action on dopaminergic functions. On the basis of the results of catalepsy and amphetamine-induced stereotypy, the compounds demonstrated an inhibitory effect on dopaminergic behaviors. However, their hypothermic effect is compatible with the stimulation of dopaminergic function which seems not to be mediated by D2/D3 receptors.
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PMID:Dopaminergic profile of new heterocyclic N-phenylpiperazine derivatives. 1271 82

SSR181507 ((3-exo)-8-benzoyl-N-(((2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl)methyl)-8-azabicyclo(3.2.1)octane-3-methanamine monohydrochloride) is a novel tropanemethanamine benzodioxane that displays antagonist activity at dopamine D(2) receptors and agonist activity at 5-HT(1A) receptors. SSR181507 antagonized apomorphine-induced climbing in mice and stereotypies in rats (ED(50) of 2 and 3.4 mg/kg i.p., respectively) and blocked D-amphetamine-induced hyperlocomotion in rats at lower doses (0.3-1 mg/kg i.p.). At 1-10 mg/kg, it was found to disrupt active avoidance in mice. SSR181507 did not induce catalepsy in rats (MED>60 mg/kg i.p.) and antagonized (3-10 mg/kg i.p.) haloperidol-induced catalepsy. SSR181507 was also active in two models sensitive to antidepressant/anxiolytic drugs: in a guinea-pig pup/mother separation test, it decreased (1-3 mg/kg i.p.) the time spent vocalizing during the separation episode, and in a lithium-induced taste aversion procedure in rats, it partially reversed (3 mg/kg i.p.) the decrease of intake of a saccharin solution. Furthermore, SSR181507 increased (3 mg/kg i.p.) the latency time to paradoxical sleep in rats, an effect commonly observed with antidepressants. Coadministration of the selective 5-HT(1A) blocker SL88.0338 produced catalepsy and antagonized the effects of SSR181507 in the depression/anxiety tests, confirming the view that activation of 5-HT(1A) receptors confers an atypical profile on SSR181507, and is responsible for its antidepressant/anxiolytic properties. Finally, SSR181507 (1-3 mg/kg) did not affect memory performance in a Morris water maze task in rats. The pharmacological profile of SSR181507 suggests that it should control the symptoms of schizophrenia, in the absence of extrapyramidal signs and cognitive deficits, with the additional benefit of antidepressant/anxiolytic activities.
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PMID:SSR181507, a dopamine D2 receptor antagonist and 5-HT1A receptor agonist. II: Behavioral profile predictive of an atypical antipsychotic activity. 1290 93

Arachidonylethanolamide (anandamide, AEA) is believed to be the endogenous ligand of the cannabinoid CB(1) and CB(2) receptors. CB(1) receptors have been found localized on fibers in the spinal trigeminal tract and spinal trigeminal nucleus caudalis. Known behavioral effects of anandamide are antinociception, catalepsy, hypothermia, and depression of motor activity, similar to Delta(9)-tetrahydocannanbinol, the psychoactive constituent of cannabis. It may be a possible therapeutic target for migraine. In this study, we looked at the possible role of the CB(1) receptor in the trigeminovascular system, using intravital microscopy to study the effects of anandamide against various vasodilator agents. Anandamide was able to inhibit dural blood vessel dilation brought about by electrical stimulation by 50%, calcitonin gene-related peptide (CGRP) by 30%, capsaicin by 45%, and nitric oxide by 40%. CGRP(8-37) was also able to attenuate nitric oxide (NO)-induced dilation by 50%. The anandamide inhibition was reversed by the CB(1) receptor antagonist AM251. Anandamide also reduced the blood pressure changes caused by CGRP injection, this effect was not reversed by AM251. It would seem that anandamide acts both presynaptically, to prevent CGRP release from trigeminal sensory fibers, and postsynaptically to inhibit the CGRP-induced NO release in the smooth muscle of dural arteries. CB(1) receptors seem to be involved in the NO/CGRP relationship that exists in causing headache and dural blood vessel dilation. It also seems that some of the blood pressure changes caused by anandamide are mediated by a noncannabinoid receptor, as AM251 was unable to reverse these effects. It can be suggested that anandamide is tonically released to play some form of modulatory role in the trigeminovascular system.
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PMID:Anandamide is able to inhibit trigeminal neurons using an in vivo model of trigeminovascular-mediated nociception. 1471 91

The results of experiments on the inheritance and neurobiological mechanism of high predisposition to tonic immobility (catalepsy) in CBA mice are discussed. Genetic analysis has demonstrated a monogenic inheritance of the predisposition to catalepsy. A set of polymorphic microsatellite markers has been used to demonstrate that the predisposition to catalepsy is linked to the distal fragment of mouse chromosome 13, which contains the gene of the 5-HT1A-serotonin receptor. Pharmacological and biochemical evidence for the association between hereditary catalepsy and 5-HT1A-receptor dysfunction are presented. The use of CBA mice for studying the mechanisms of depression and the effects of antidepressants is discussed.
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PMID:[Hereditary catalepsy: genetic and molecular mechanisms of catalepsy in mice]. 1534 Dec 68


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