• The Korean Journal of Pain
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• v.29 no.3
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• pp.164-171
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• 2016

Background: Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. Methods: The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. Results: When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. Conclusions: Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.24 no.1
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• pp.21-27
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• 2013

Objectives : Dysregulation of the central noradrenergic system may be involved in the pathophysiology of attention-deficit hyperactivity disorder (ADHD). The aim of this study was to examine the differences in pre- and post-treatment cerebral perfusion according to the MspI polymorphisms of the alpha-2A-adrenergic receptor gene (ADRA2A) in children with ADHD. Methods : Thirty seven drug-naive ADHD children (8.9+1.8 years old, M=32, F=5) were genotyped. Baseline single-photon emission computed tomography (SPECT) and clinical assessments were performed for ADHD children. After treatment with methylphenidate for eight weeks, SPECT and clinical assessment were repeated. Results : No differences in baseline clinical assessments or cerebral perfusion were observed according to the MspI genotype. However, after treatment, ADHD children with the G/G genotype at the MspI polymorphism showed hyperperfusion in the right cerebellar declive (p=.001, uncorrected) and hypoperfusion in the left lentiform nucleus and left cingulate gyrus (p<.001 and p=.001, uncorrected), compared to children without the G/G genotype. Conclusion : Although the results of this study should be interpreted cautiously, they suggest a possible role of the MspI polymorphisms of the ADRA2A gene in methylphenidate-induced changes in cerebral perfusion.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.29-37
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• 1994

Inhibition of the nociceptive Tail Flick Reflex (TFR) was observed with electrical stimulation of the locus coeruleus/subcoeruleus (LC/SC) in the male Sprague - Dawley rats under light anesthesia, and the involved neurotransmitter (s) were characterized. Electrical stimulation of LC/SC induced the analgesia with the stimulation threshold (intensity of the current, given for 100 usec and in 100 Hz frequency, which caused the TF latency longer than 6.5 sec) around 55 uA. Intrathecal administrations of ${\alpha}_2$ antagonist, yohimbine (30 ug) or opioid antagonist, naloxone (20 ug) increased the stimulation threshold by 147% and 123% respectively (from 55 uA to 135 uA,9 and from 54 uA to 123 uA;P0.01, n=5, each). The basal TF latency without stimulation (3.1 sec) was reduced by the antagonists (to 2.5 sec by yohimbine, p<0.05, n=5; to 2.6 sec by naloxone, p<0.1, n=5), vehicle only did not show any effect. Noradrenaline(NA) in the spinal cord superfusates measured with HPLC was increased by the LC/SC stimulation, from 4.18 ng/ml before to 7.74 ng/ml after stimulation (P<0.05, n=10). The result suggest that analgesia induced by LC/SC stimulation is mediated, at least in part, by the noradrenergic system in which ${\alpha}_2$ receptor is involved, as well as the opioid system.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.153-160
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• 1999

Animal models can provide a useful tool for the study of some aspects of psychiatric disorders and their treatment. The four criteria for the evaluation of animal models of psychiatric disorders are as following : 1) similarity of inducing conditions 2) similarity of behavioral state 3) common underlying neurobiological mechanisms 4) reversal by clinically effective treatment techniques. Several animal models have been proposed for schizophrenia : phenylethylamine model, L-dopa model, hallucinogen model, cocaine model, amphetamine model, phencyclidine model, noradrenergic reward system lesion model, reticular stimulation model, social isolation model, conditioned avoidance reaction, catalepsy test, paw test, self-stimulation paradigms, latent inhibition paradigms, blocking paradigms, prepulse inhibition of the startle reflex, rodent interaction, social behavior in monkeys, hippocampal damage, high ambient pressure, and models using selective breeding. Among them, animals with bilateral lesion of the hippocampus may provide an adequate animal model for several symptoms of schizophrenia, and ketamine model can reproduce negative symptoms and cognitive deficits as well as positive symptoms of schizophrenia. In conclusion, no model of schizophrenia is entirely representative of the disease, and findings gleaned from model systems must be cautiously interpreted. Furthermore, the process of developing and validating animal models must work in concert with the process to identify reliable measures of human phenomenology.