• The Korean Journal of Pharmacology
• /
• v.11 no.1 s.17
• /
• pp.55-60
• /
• 1975

An animal which is placed in a new environment displays a complex behavioral pattern consisting of locomotion, grooming and rearing. This behavioral pattern is influenced by endogenous and exogenous stimuli, such as hormonal secretion, level of neurohumoral transmitters, drugs and light. It is widely known that the most tranquilizers depressed spontaneous motor activity although their mechanisms of action were different, while antidepressants stimulated except imipramine which showed various action. Until the present time, the hole-board apparatus, which gives rather subjective data, has been used extensively to study the effects of drugs on general activity and exploratory behavior in mice. Recently a new apparatus for mobility measurements, called a 'Selective Activity Meter' has been introduced. This instrument supposedly produces more objective data on activity and behavior. The purpose of the present experiment was to study the influence of psychotropics on motor activity using the Selective Activity Meter. In the experiment, various psychotropic agents such as major tranquilizers(chlorpromazine, haloperidol); minor tranquilizers(meprobamate, diazepam); and antidepressants(amphetamine, imipramine) were used. In each experiment, the drug was administered to five mice and their activity was recorded. Each experiment was run five or more times and the results are based on the mean of each trial. The results are summarized as follows: 1. The group of mice treated with chlorpromazine showed markedly inhibited motor activity in comparison with controls and the inhibitory action of chlorpromazine was shown to be more intense than any of the other drugs used in the test. Haloperidol administration yielded similar results until 60 minutes, but mice showed less inhibition of motor activity than with chlorpromazine after 90 minutes. 2. In the group treated with diazepam, there was strong inhibition of motor activity until 30 minutes, but after 60 minutes the mice showed less inhibition than with chlorpromazine. In the meprobamate group, motor activity was inhibited in a manner similar to that of other tranquilizers, but the inhibition was less than that of diazepam. 3. In the group treated with imipramine, the inhibition developed gradually after ten minutes. 4. The effects of amphetamine did not appear until 30 minutes after administration, but then there was a significant increase in the motor activity.

• Korean Journal of Biological Psychiatry
• /
• v.8 no.1
• /
• pp.85-95
• /
• 2001

This study was designed to examine the effects of two antidepressant drugs on the expression of c-fos mRNA in cultured embryonic rat hippocampal neurons. The drugs used were imipramine and amitriptyline. On the fourth day of culture, hippocampal neurons were treated with variable concentrations of each drug. Competitive RT-PCR(Reverse Transcriptase-PCR) analysis was used to quantify the c-fos mRNA expression induced by each drug. Experimental results showed that acute and direct treatment with imipramine and amitriptyline with relatively low concentrations(imipramine ${\leq}10{\mu}M$, amitriptylne ${\leq}10{\mu}M$) had no inductive effect on the expression of c-fos mRNA in the rat hippocampal neurons. However, after treatment with relatively high concentrations(imipramine ${\geq}100{\mu}M$, amitriptyline ${\geq}100{\mu}M$) c-fos mRNA was not detected. These findings suggest the followings. Firstly, the action mechanisms of these drugs on the hippocampal neurons might not be mediated by c-fos but by other immediate-early genes(IEGs). Secondly, their actions may be mediated indirectly via other areas of the brain. Thirdly, the expression of c-fos might be inhibited by high concentrations of these drugs, or the high concentrations could induce cell death. Finally, though cell death remains to be confirmed, the inhibition of c-fos induction or cell death could play a role in the cognitive impairments known to be adverse effects of some antidepressants. This study is believed to be a first step toward understanding the mechanisms of learning and memory. Further studies are needed to investigate the expression of various IEGs and changes in the hippocampal neurons of rat resulting from chronic treatment with antidepressant drugs.

• 대한임상약리학회:학술대회논문집
• /
• 1994.12a
• /
• pp.27-27
• /
• 1994

• 대한임상약리학회:학술대회논문집
• /
• 1997.12a
• /
• pp.42-42
• /
• 1997

• Korean Journal of Biological Psychiatry
• /
• v.5 no.1
• /
• pp.134-137
• /
• 1998

Authors report a case of separation anxiety disorder, which developed as a side effect during haloperidol treatment of Tourette syndrome(TS). In this case, 14 years old boy developed attention deficit symptoms during his infancy. At 4th grade of primary school, he developed vocal tic, motor tic, and coprolalia. With 5mg/day of haloperidol treatment his symptoms of TS were subsided. During the treatment, he developed features of separation anxiety disorder, including dependence, pleading, clinging, and sadness. Symptoms of attention deficit and separation anxiety disorder were improved by 25mg/day of imipramine treatment. During haloperidol treatment of TS, careful observation may be needed whether separation anxiety disorder-like symptom develops.

• The Korean Journal of Pharmacology
• /
• v.12 no.1
• /
• pp.15-22
• /
• 1976

The clinical abuse of C.N.S. stimulants during recent years has directed particular attention. Effect of various organs other than C.N.S. was also extensively investigated with those agents. It has been shown that, although there is a wide variation in sensitivity between species, caffeine stimulates gastric secretion in man, cat, guinea pig and dog. Roth and Ivy(1944) reported that caffeine and histamine acted synergistically in stimulating gastric secretion in the cat. Vaille et al(1966) studied that production of pancreatic juice in the rat was enhanced, but bile secretion was not affected by caffeine. In clinical study the effect of chlorpromazine on the external pancreatic secretion in the 24 subjects, the volume fell more than 20% in 7 subjects. (Skajaa et al 1960) It is widely known that C.N.S. stimulants enhanced spontaneous motor activity in the mice, while tranquilizers depressed the activity. Woo (1975) reported that the group of mice treated with chlorpromazine showed markedly inhibited motor activity and in the group of mice treated with amphetamine, there was a significant increase in the motor activity. The purpose of the present experiment was to study the effects of C.N.S. stimulants and depressant on the exocrine pancreas, and on the spontaneous motor activity in the rats. The results obtained are summarized as follows. 1. In animals treated with xanthine derivatives, the volume of pancreatobiliary secretion was markedly increased. 2. Total bilirubin output was elevated markedly in the xanthine derivatives and imipramine treated animals. The bilirubin concentration was increased in xanthine derivatives treated group. 3. The concentration of cholate in the bile was decreased in the chlorpromazine treated group. 4. The activity of lipase in the pancreatobiliary juice was elevated markedly in the xanthine derivatives treated group only. 5. In the all experimental groups, the activity of amylase in pancreatobiliary juice was significantly elevated. 6. In the caffeine treated group, spontaneous motor activity was markedly increased in $30{\sim}60$ minutes, and the amphetamine treated group showed the increased motor activity in first 30 minutes. 7. The group of rats treated with chlorpromazine showed markedly inhibited motor activity after 30 minutes, and the imipramine treated group showed similar result but less inhibition.

• Journal of Ginseng Research
• /
• v.44 no.4
• /
• pp.603-610
• /
• 2020

Background: Depression is a common neuropsychiatric disease that shows astrocyte pathology. Ginsenoside Rf (G-Rf) is a saponin found in Panax ginseng which has been used to treat neuropsychiatric diseases. We aimed to investigate antidepressant properties of G-Rf when introduced into the L-alphaaminoadipic acid (L-AAA)-infused mice model which is representative of a major depressive disorder that features diminished astrocytes in the brain. Methods: L-AAA was infused into the prefrontal cortex (PFC) of mice to induce decrease of astrocytes. Mice were orally administered G-Rf (20 mg/kg) as well as vehicle only or imipramine (20 mg/kg) as controls. Depression-like behavior of mice was evaluated using forced swimming test (FST) and tail suspension test (TST). We observed recovery of astroglial impairment and increased proliferative cells in the PFC and its accompanied change in the hippocampus by Western blot and immunohistochemistry to assess the effect of G-Rf. Results: After injection of L-AAA into the PFC, mice showed increased immobility time in FST and TST and loss of astrocytes without significant neuronal change in the PFC. G-Rf-treated mice displayed significantly more decreased immobility time in FST and TST than did vehicle-treated mice, and their immobility time almost recovered to those of the sham mice and imipramine-treated mice. G-Rf upregulated glial fibrillary acidic protein (GFAP) expression and Ki-67 expression in the PFC reduced by L-AAA and also alleviated astroglial change in the hippocampus. Conclusion: G-Rf markedly reversed depression-like behavioral changes and exhibited protective effect against the astrocyte ablation in the PFC induced by L-AAA. These protective properties suggest that G-Rf might be a therapeutic agent for major depressive disorders.

• The Korean Journal of Physiology and Pharmacology
• /
• v.3 no.1
• /
• pp.59-68
• /
• 1999

Chemically induced hypoxia has been shown to induce a depletion of ATP. Since intracellular free $Mg^{2+}\;([Mg^{2+}]_i)$ appears to be tightly regulated following cellular energy depletion, we hypothesized that the increase in $[Mg^{2+}]_i$ would result in $Mg^{2+}$ extrusion following hormonal stimulation. To determine the relation between $Mg^{2+}$ efflux and cellular energy state in a hypoxic rat heart and isolated myocytes, $[Mg^{2+}]_i,$ ATP and $Mg^{2+}$ content were measured by using mag-fura-2, luciferin-luciferase and atomic absorbance spectrophotometry. $Mg^{2+}$ effluxes were stimulated by norepinephrine (NE) or cAMP analogues, respectively. $Mg^{2+}$ effluxes induced by NE or cAMP were more stimulated in the presence of metabolic inhibitors (MI). Chemical hypoxia with NaCN (2 mM) caused a rapid decrease of cellular ATP within 1 min. Measurement of $[Mg^{2+}]_i$ confirmed that ATP depletion was accompanied by an increase in $[Mg^{2+}]_i.$ No change in $Mg^{2+}$ efflux was observed when cells were incubated with MI. In the presence of MI, the cAMP-induced $Mg^{2+}$ effluxes were inhibited by quinidine, imipramine, and removal of extracellular $Na^+.$ In addition, after several min of perfusion with $Na^+-free$ buffer, a large increase in $Mg^{2+}$ efflux occurred when $Na^+-free$ buffer was switched to 120 mM $Na^+$ containing buffer. A similar $Mg^{2+}$ efflux was observed in myocytes. These effluxes were inhibited by quinidine and imipramine. These results indicate that the activation of $Mg^{2+}$ effluxes by hormonal stimulation is directly dependent on intracellular $Mg^{2+}$ contents and that these $Mg^{2+}$ effluxes appear to occur through the $Na^+-dependent\;Na^+/Mg^{2+}$ exchange system during chemical hypoxia.

• The Korean Journal of Physiology and Pharmacology
• /
• v.2 no.3
• /
• pp.307-312
• /
• 1998

This study was performed to investigate the mechanism of central analgesic effects of antidepressants. Thirty four male rats were anesthetized with pentobarbital sodium (40 mg/kg, ip). A stainless steel guide cannula and a PE tube (PE10) were implanted into the lateral ventricle and cisterna magna area. Stimulating and recording electrodes were implanted into the incisor pulp and anterior digastric muscle. Electrodes were led subcutaneously to the miniature cranial connector sealed on the top of the skull with acrylic resin. The jaw opening reflex was used in freely moving rats, and antidepressants were administered intracisternally in order to eliminate the effects of anesthetic agents on the pain assessment and evaluate the importance of the central action site of antidepressants. After 48 hours of recovery from surgery, digastric electromyogram (dEMG) of freely moving rats was recorded. Electrical shocks (200 ${\mu}sec$ duration, 0.5-2 mA intensity) were delivered at 0.5 Hz to the dental pulp every 2 minute. Intracisternal administration of $15\;{\mu}g$ imipramine suppressed dEMG elicited by noxious electrical stimulation in the tooth pulp to $76{\pm}6%$ control. Intracisternal administration of $30\;{\mu}g$ desipramine, nortriptyline, or imipramine suppressed dEMG remarkably to $48{\pm}2,\;27{\pm}8,\;or\;25{\pm}5%$ of the control, respectively. Naloxone, methysergide, and phentolamine blocked the suppression of dEMG produced by intracisternal antidepressants from $23{\pm}2\;to\;69{\pm}4%,\;from\;32{\pm}5\;to\;80{\pm}9%,\;and\;from\;24{\pm}6\;to\;77{\pm}5%$ of the control, respectively. These results indicate that antidepressants produce antinociception through central mechanisms in the orofacial area. Antinociception of intracisternal antidepressants seems to be mediated by an augmentation of descending pain inhibitory influences on nociceptive pathways.

• CELLMED
• /
• v.9 no.1
• /
• pp.1.1-1.13
• /
• 2019

Background: Contents of bioactive substances extractable from different parts of terrestrial plants vary enormously. Aim: To ascertain that parts of Withania somnifera other than its roots can also be used for prevention and cure of unavoidable stress triggered central hypersensitivity to pain. Material and Methods: Groups of male or female mice treated either with Withania somnifera extracts or with metformin, aspirin, imipramine, diazepam and niacin for 11 consecutive days were subjected to "foot-shock stress-induced hyperthermia" and "hot plate" tests on the 1st, 5th, 7th, and 10th days of the experiments. On the 11th day, they were subjected to tail suspension test and on 12th day pentobarbital hypnosis test. Results: Except for diazepam and imipramine, protective effects of all other tested drugs as well as of the Withania somnifera extracts against stress-induced central hypersensitivity to pain were accompanied by their preventive effects against foot-shock stress-induced body weight losses. All observed stress response suppressing effects of all test agents increased with increasing numbers of treatment days. However, mean duration of pentobarbital-induced sleep was shorter in the extracts treated groups and longer in the diazepam treated ones only. Conclusions: Reported observations reveal that pharmacological activity profile of Withania somnifera extracts in male and female mice are almost identical, and are not like those of several drugs currently often prescribed for the treatment of diabetes-associated comorbidities. Withanolides are not the only extractable bioactive constituents of Withania somnifera. The described bioassay system is well suited for pharmacological standardization of diverse types of Withania somnifera extracts.