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

The influence of choline- and serotoninergic agents on the pedal self-stimulation (SS) was studied in male rats of Wistar line. Physostigmine decreased the frequency of pressing on the pedal whereas fluoxetine didn't influence SS. Scopolamine activated SS and lowered the threshold of the SS-reaction. P-chloroamphetamine effect depended on the action phase of the drug and was manifested both in depression and activation of SS. Preliminary administration of fluoxetine decreased the activating effect of scopolamine and enhanced the depressing effect of physostigmine. A combination of p-chloroamphetamine and cholinergic agents was accompanied by a tendency toward weakening of depressing effect of physostigmine and toward enhancing of activating effect of scopolamine. It is suggested that serotoninergic mechanisms in case of changes in activity of cholinergic processes, depress the system of positive reinforcement. A functional interaction of choline- and serotoninergic neurotransmitter systems seems probable.
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PMID:[Effect of cholin- and serotoninergic substances on self stimulation in rats]. 22 89

The effect of tetanic activation of corticostriatal glutamatergic fibers was studied in striatal slices by utilizing extracellular and intracellular recording techniques. Tetanic stimulation produced a long-term synaptic depression (LTD) (> 2 h) of both extracellularly recorded field potentials and intracellularly recorded EPSPs. LTD was not coupled with changes of intrinsic membrane properties of the recorded neurons. In some neurons, repetitive cortical activation produced a short-term posttetanic potentiation (1-3 min). Subthreshold tetanic stimulation, which under control condition did not cause LTD, induced LTD when associated with membrane depolarization. Moreover, LTD was not expressed in cells in which the conditioning tetanus was coupled with hyperpolarization of the membrane. Bath application of aminophosphonovalerate (30-50 microM), an antagonist of NMDA receptors, did not affect the amplitude of the synaptic potentials and the expression of LTD. Striatal LTD was significantly reduced by the pretreatment of the slices with 30 microM 2-amino-3-phosphonopropionic acid, an antagonist of glutamate metabotropic receptors. LTD was not blocked by bicuculline (30 microM), a GABA(A) receptor antagonist. Scopolamine (3 microM), an antagonist of muscarinic receptors, induced a slight, but significant, increase of the amplitude of LTD. Both SCH 23390 (3 microM), an antagonist of D1 dopamine (DA) receptors, and I-sulpiride (1 microM), an antagonist of D2 DA receptors, blocked LTD. LTD was also absent in slices obtained from rats in which the nigrostriatal DA system was lesioned by unilateral nigral injection of 6-hydroxydopamine. In DA-depleted slices, LTD could be restored by applying exogenous DA (30 microM) before the conditioning tetanus. In DA-depleted slices, LTD could also be restored by coadministration of SKF 38393 (3-10 microM), a D1 receptor agonist, and of LY 171555 (1-3 microM), a D2 receptor agonist. Application of a single class of DA receptor agonists failed to restore LTD. These data show that striatal LTD requires three main physiological and pharmacological conditions: (1) membrane depolarization and action potential discharge of the postsynaptic cell during the conditioning tetanus, (2) activation of glutamate metabotropic receptors, and (3) coactivation of D1 and D2 DA receptors. Striatal LTD may alter the output signals from the striatum to the other structures of the basal ganglia. This form of synaptic plasticity can influence the striatal control of motor activity.
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PMID:Long-term synaptic depression in the striatum: physiological and pharmacological characterization. 135 31

1. The anticholinergic drug N-ethyl-2-pyrrolidylmethylcyclopentylphenyl glycollate (PMCG) has been studied for its effects on the contraction of fast-twitch (flexor hallucis longus, FHL) and slow-twitch (soleus) muscles in the cat.2. In both muscles lower doses (0.25 to 10 mg intra-arterially) potentiated and higher doses (10 mg and above) depressed twitches produced by indirect stimulation. Similar effects were obtained in directly stimulated muscles.3. The effects of the drug on muscles stimulated repetitively were dependent on both dose and frequency of stimulation. Doses which potentiated twitches also potentiated low frequency tetani (5-30 Hz for soleus; 10-50 Hz for FHL). There was a depression and non-maintenance of higher frequency tetani (80 Hz and above for soleus; 150 Hz and above for FHL).4. Both atropine and caramiphen had similar dose dependent potentiating and depressant actions. Hyoscine acted similarly in some cats; in others it had only a depressant action.5. It is suggested that the potentiating actions of PMCG, caramiphen, atropine and hyoscine are due to a direct musculotropic action. The depressant actions resulting from higher doses are due, in part, to a curare-like action and in part to a direct action on the muscle fibres.
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PMID:Actions of some cholinergic antagonists on fast-twitch and slow-twitch skeletal muscle of the cat. 548 23

Increasing doses of pilocarpine, 100-400 mg/kg, were given intraperitoneally to mice and the resulting behavioral, electroencephalographic and neuropathological alterations were studied. No behavioral phenomena were observed in mice treated with the lowest dose of pilocarpine. Occasional tremor and myoclonus of hindlimbs were found in animals which received pilocarpine in a dose of 200 mg/kg. At doses of 300, 325 and 350 mg/kg, pilocarpine produced a sequence of behavioral alterations including staring spells, limbic gustatory automatisms and motor limbic seizures that developed over 15-30 min and built up progressively into a limbic status epilepticus lasting for several hours. The highest dose of pilocarpine, 400 mg/kg, was generally lethal to mice. Pilocarpine produced both interictal and ictal epileptiform activity in the electroencephalogram (EEG). The earliest EEG alterations appeared in the hippocampus and then spread to cortical areas. EEG seizures started 10-15 min after injection of large doses of pilocarpine, 300-350 mg/kg. Ictal periods lasted for 1-2 min, recurred every 5-10 min and were followed by periods of depression of the EEG activity. By 30-45 min paroxysmal activity resulted in a status epilepticus. Examination of frontal forebrain sections with light microscopy revealed a widespread damage to several brain regions including the hippocampus, amygdala, thalamus, olfactory cortex, neocortex and substantia nigra. Scopolamine, 10 mg/kg, and diazepam, 10 mg/kg, prevented the development of convulsive activity and brain damage produced by pilocarpine. The results emphasize that excessive and sustained stimulation of cholinergic receptors can lead to seizures and seizure-related brain damage in mice. It is proposed that systemic pilocarpine in mice provides a useful animal model for studying mechanisms of and therapeutic approaches to temporal lobe epilepsy.
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PMID:Seizures produced by pilocarpine in mice: a behavioral, electroencephalographic and morphological analysis. 649 17

Adult male Sprague-Dawley rats were subjected to acute (95 dB white noise) or chronic stress, or their combination. In comparison with unstressed controls, stressed rats were more active upon several measures of open field activity. A history of chronic stress eliminated the acute stress induced activation. Concurrent treatment of chronically stressed rats with amitriptyline or scopolamine, or with a combination of both drugs resulted in selective behavioral improvement (i.e., in motor activity, latency, defecation) for amitriptyline and combined treatment rats, with significant restoration of the normal behavioral response. Scopolamine however was only marginally effective. A higher dose of scopolamine proved effective, but only with a marked disruption of baseline activity. Examination of plasma corticosterone titers indicated that chronic stress induced an elevation of basal levels and that this was reversed by amitriptyline, scopolamine, and combined drug treatment. Thus while behavioral depression and elevated corticosteroids may covary they are not identically mediated.
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PMID:Amitriptyline and scopolamine in an animal model of depression. 719 57

The effect of exogenous choline on the outflow of 3H-acetylcholine evoked by field stimulation was studied on the myenteric plexus-longitudinal muscle preparation of the guinea pig. Choline at concentrations of 100 microM and higher depressed the evoked outflow of 3H-acetylcholine in a concentration-dependent manner. The EC50 for the inhibitory action was 300 microM. Scopolamine (10 nM) antagonized the effect of choline which indicates that the inhibition of 3H-acetylcholine outflow is mediated by muscarine receptors. The findings imply that choline at high concentrations does not improve cholinergic synaptic neurotransmission in tissues that are endowed with presynaptic muscarine receptors (e.g. myenteric and central cholinergic neurones). Furthermore, it is suggested that the increase in tissue acetylcholine content that has been observed after choline administration is probably due to the depression of acetylcholine release.
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PMID:Choline inhibits acetylcholine release via presynaptic muscarine receptors. 724 99

Premedication of patients requiring cardiac surgery should provide adequate analgesia, sedation and anxiolysis for the stress and pain associated with preoperative preparation and placement of monitoring catheters. Ideally, these effects would be achieved without producing respiratory depression and hypoxia, which could be life-threatening to patients at risk for myocardial ischemia. Ketorolac, a nonsteroidal, antiinflammatory agent, has previously been shown to provide postoperative pain relief comparable to that provided by morphine, without respiratory depression. This study compared the incidence of arterial blood desaturation, respiratory depression, and patient comfort after preoperative medication with scopolamine and ketorolac versus scopolamine and morphine. Scopolamine and ketorolac premedication provided sedation and analgesia comparable to that provided by scopolamine and morphine, without significant respiratory depression. Since ketorolac has no central respiratory depressant effect, it may be a useful alternative to morphine for premedication in the cardiac surgical patient.
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PMID:Ketorolac as a premedicant for coronary artery bypass surgery patients with normal ventricles. 813 95

Anticholinergics, benzodiazepines and N-methyl-D-aspartate (NMDA) antagonists have been shown to modulate the expression of nerve agent-induced seizures. This study examined whether the anticonvulsant actions of these drugs varied depending on the duration of prior seizure activity. Rats implanted with electrodes to record electroencephalographic (EEG) activity were pretreated with the oxime HI-6 (125 mg/kg, IP) to prolong survival, and then challenged with a convulsant dose of the nerve agent soman (180 micrograms/kg, SC); treatment compounds (scopolamine, diazepam, MK-801, atropine, benactyzine, and trihexyphenidyl) were delivered IV at specific times after seizure onset. Both diazepam and MK-801 displayed a similar profile of activity: At both short or long times after seizure initiation the anticonvulsant efficacy of each drug remained the same. Diazepam, and especially MK-801, enhanced the lethal actions of soman by potentiating the respiratory depressant effects of the agent; scopolamine given prior to diazepam or MK-801 protected against the respiratory depression. Scopolamine and atropine showed a dose- and time-dependent effectiveness; the longer the seizure progressed the higher the dose of drug required to terminate the seizure, with eventual loss of anticonvulsant activity if the seizure had progressed for 40 min. In contrast, benactyzine and trihexyphenidyl showed a third profile of activity: There was a smaller increase in drug dosage required for anticonvulsant activity as seizure duration increased, and both drugs could terminate seizures that had progressed for 40 min. The early anticonvulsant action of anticholinergics is interpreted as a specific effect that blocks the primary cholinergic excitatory drive that initiates, and first maintains, nerve agent seizures. If allowed to progress, the seizure activity itself recruits excitatory neurotransmitter systems (i.e., NMDA) that eventually maintain the seizure independent of the initial cholinergic drive. This is indicated by the eventual ineffectiveness of scopolamine and atropine as the duration of the seizure progresses. Diazepam and MK-801 appear to act to moderate nerve agent seizures by enhancing inhibitory activity (diazepam) or dampening the secondarily activated noncholinergic excitatory system (MK-801). Benactyzine and trihexyphenidyl represent compounds that possibly have both anticholinergic and NMDA antagonistic properties.
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PMID:Pharmacological modulation of soman-induced seizures. 851 3

We examined the effects of p.o. administered 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-b enzazepin-8- yl)-1-propanone fumarate (TAK-147), a novel AChE inhibitor, on impaired learning and memory in animal models. At 1 to 3 mg/kg, TAK-147 ameliorated the passive avoidance deficit induced by diazepam. TAK-147 did not affect delayed-matching-to-position (DMTP) performance of normal rats at doses of 1 to 30 mg/kg assessed by using a three-lever operant chamber, but 9-amino-tetrahydroacridine disrupted the DMTP response at 5 to 20 mg/kg. Scopolamine (0.02-0.1 mg/kg s.c.) impaired DMTP performance, whereas methylscopolamine did not affect the DMTP task. TAK-147 ameliorated the impairment of DMTP performance induced by scopolamine without affecting the general behavior of the rats; however, 9-amino-tetrahydroacridine produced no significant amelioration of the impairment. The intraventricular injection of AF64A disrupted differential-reinforcement-of-low-rate 10-sec performance in rats, as demonstrated by marked decreases in reinforcement rate and response efficiency. TAK-147 slightly increased the reinforcement rate in AF64A-treated rats at a low dose of 1 mg/kg, but the effect was not significant statistically. TAK-147 had no significant effect on the duration of immobility in rats in a forced swimming test at doses of 2 to 10 mg/kg. 9-Amino-tetrahydroacridine prolonged the duration of immobility at 5 to 20 mg/kg. Furthermore, TAK-147 reversed reserpine-induced hypothermia and ptosis in mice at doses of 3 to 10 mg/kg, a result that implies an antidepressant-like action. These results indicate that TAK-147 ameliorates learning and memory impairment in animal models without affecting the general behavior or causing behavioral depression and suggest that TAK-147 may be useful for the treatment of Alzheimer's disease.
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PMID:Effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1 -H-1-benzazepin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase inhibitor, on impaired learning and memory in animal models. 866 90

The degree of cholinergic dysregulation of sleep in adult depression was evaluated using scopolamine. On separate sessions, placebo and scopolamine (4.5 micrograms/kg, IM) were administered to 14 patients with unipolar major depression, 16 recovered/remitted patients, and 18 normal controls. Scopolamine increased rapid eye movement (REM) latency (RL), reduced REM activity (RA), REM density (RD), and REM duration, and increased the percentage of stage 4 sleep in all groups. There was a differential effect of scopolamine on RL, RA, and REM duration for the first REM period, and on percentage of stage 4 sleep. Whereas a primary cholinergic hyperactivity could account for the RA and RD responses, the response profile for RL was more compatible with reduced aminergic tone as the proximal cause of the cholinergic hyperactivity. Whether the sleep abnormalities observed in remitted patients reflect an underlying vulnerability for development or recurrence of depression, and/or a scar, remains to be determined.
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PMID:Differential response of rapid eye movement sleep to cholinergic blockade by scopolamine in currently depressed, remitted, and normal control subjects. 911 98


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