The Experts below are selected from a list of 288 Experts worldwide ranked by ideXlab platform
Masahiro Shibasaki - One of the best experts on this subject based on the ideXlab platform.
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The K + -Cl − Cotransporter KCC2 and Zolpidem
Neuropathology of Drug Addictions and Substance Misuse, 2016Co-Authors: Masahiro Shibasaki, Tomohisa Mori, Tsutomu SuzukiAbstract:Zolpidem is a short-acting nonbenzodiazepine that is prescribed to treat insomnia, and it also induces Psychological Dependence. Zolpidem binds to the benzodiazepine binding site that is located on the GABA A receptor, and activation of the GABA A receptor by GABA results in an increase in Cl − influx. Cl − homeostasis in neurons is also modulated by KCC2, which can regulate Cl − efflux to equilibrate the membrane potential in mature neurons. Thus, it is possible that continuous Cl − influx via stimulation of the GABA A receptor may also affect the efflux of Cl − as KCC2 in Cl − homeostasis. In this chapter we will describe the role of KCC2 in Psychological Dependence by chronic treatment with zolpidem.
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upregulation of l type cav1 channels in the development of Psychological Dependence
Synapse, 2010Co-Authors: Masahiro Shibasaki, Kazuhiro Kurokawa, Seitaro OhkumaAbstract:Although L-type voltage-dependent Ca2+ channels regulate activity-dependent processes including synaptic plasticity and synapse formation, there are few data on the changes of Cav1 channel expression in Psychological Dependence. This study investigated the role of L-type Cav1 channel expression in the brain of mouse that was Psychologically dependent on methamphetamine (2 mg/kg, subcutaneous injection [s.c.]), cocaine (10 mg/kg, s.c.), and morphine (5 mg/kg, s.c.) with the conditioned place preference paradigm. Intracerebroventricular administration of nifedipine (3, 10, and 30 nmol/mouse) dose-dependently reduced the development of methamphetamine-, cocaine-, and morphine-induced rewarding effect. Under such conditions, protein levels of both Cav1.2 and Cav1.3 in the frontal cortex and the limbic forebrain were significantly increased on methamphetamine-, cocaine-, and morphine-induced Psychologically dependent mice. These findings suggest that the upregulation of Cav1.2 and Cav1.3 participated in the development of Psychological Dependence. Synapse 64:440–444, 2010. © 2010 Wiley-Liss, Inc.
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Upregulation of L‐type Cav1 channels in the development of Psychological Dependence
Synapse (New York N.Y.), 2010Co-Authors: Masahiro Shibasaki, Kazuhiro Kurokawa, Seitaro OhkumaAbstract:Although L-type voltage-dependent Ca2+ channels regulate activity-dependent processes including synaptic plasticity and synapse formation, there are few data on the changes of Cav1 channel expression in Psychological Dependence. This study investigated the role of L-type Cav1 channel expression in the brain of mouse that was Psychologically dependent on methamphetamine (2 mg/kg, subcutaneous injection [s.c.]), cocaine (10 mg/kg, s.c.), and morphine (5 mg/kg, s.c.) with the conditioned place preference paradigm. Intracerebroventricular administration of nifedipine (3, 10, and 30 nmol/mouse) dose-dependently reduced the development of methamphetamine-, cocaine-, and morphine-induced rewarding effect. Under such conditions, protein levels of both Cav1.2 and Cav1.3 in the frontal cortex and the limbic forebrain were significantly increased on methamphetamine-, cocaine-, and morphine-induced Psychologically dependent mice. These findings suggest that the upregulation of Cav1.2 and Cav1.3 participated in the development of Psychological Dependence. Synapse 64:440–444, 2010. © 2010 Wiley-Liss, Inc.
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Glutamatergic neurotransmission and protein kinase C play a role in neuron-glia communication during the development of methamphetamine-induced Psychological Dependence.
The European journal of neuroscience, 2005Co-Authors: Mayumi Miyatake, Masahiro Shibasaki, Minoru Narita, Atsushi Nakamura, Tsutomu SuzukiAbstract:Methamphetamine (METH) is a strongly addictive psychostimulant that dramatically affects the central nervous system (CNS). On the other hand, protein kinase C (PKC) plays a major role in cellular regulatory and signalling processes that involve protein phosphorylation. The purpose of this study was to investigate the role of neuronal and astrocytic PKC in changes in the central glutamatergic system induced by METH. We show here that in vitro treatment with METH caused the phosphorylation of both neuronal and astrocytic PKC and the activation of astrocytes in cortical neuron/glia co-cultures. Treatment of cortical neuron/glia co-cultures with either the PKC activator phorbol 12,13-dibutyrate (PDBu) or glutamate also caused the PKC-dependent activation of astrocytes. The PKC inhibitor chelerythrine suppressed the Ca2+ responses to glutamate in both cortical neurons and astrocytes. Moreover, a low concentration of PDBu significantly enhanced the Ca2+ responses to glutamate, but not to dopamine, in both cortical neurons and astrocytes. Notably, treatment with METH also enhanced the Ca2+ responses to glutamate in cortical neurons. The activation of astrocytes induced by METH was also reversed by co-treatment with glutamate receptor antagonists (ifenprodil, DNQX or MPEP) in cortical neuron/glia co-cultures. In the conditioned place preference paradigm, intracerebroventricular administration of glutamate receptor antagonists (ifenprodil, DNQX or MPEP) attenuated the METH-induced rewarding effect. These findings provide evidence that the changes in PKC-dependent neuronal and astrocytic glutamatergic transmission induced by METH may, at least in part, contribute to the development of Psychological Dependence on METH.
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Implication of cyclin-dependent kinase 5 in the development of Psychological Dependence on and behavioral sensitization to morphine
Journal of Neurochemistry, 2005Co-Authors: Minoru Narita, Yasuyuki Nagumo, Masahiro Shibasaki, Michiko Narita, Yoshinori Yajima, Tsutomu SuzukiAbstract:In the present study, we investigated the role of cyclin-dependent kinase 5 (cdk5) in the brain dynamics changed by repeated in vivo treatment with morphine. The level of phosphorylated-cdk5 was significantly increased in the cingulate cortex of mice showing the morphine-induced rewarding effect. Under these conditions, roscovitine, a cdk5 inhibitor, given intracerebroventricularly (i.c.v.) caused a dose-dependent and significant inhibition of the morphine-induced rewarding effect. In addition, the dose–response effect of the morphine-induced rewarding effect was dramatically attenuated in cdk5 heterozygous (+/–) knockout mice. Furthermore, the development of behavioral sensitization by intermittent administration of morphine was virtually abolished in cdk5 (+/–) mice. These findings suggest that the induction and/or activation of cdk5 are implicated in the development of Psychological Dependence on morphine.
Hossein Miladi-gorji - One of the best experts on this subject based on the ideXlab platform.
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Saffron (Crocus sativus L.) stigma reduces symptoms of morphine-induced Dependence and spontaneous withdrawal in rats.
The American journal of drug and alcohol abuse, 2021Co-Authors: Benyamin Kiashemshaki, Ali Khaleghian, Ali Ghanbari, Hossein Ali Safakhah, Hossein Miladi-gorjiAbstract:Background: Chronic morphine induces physical and Psychological Dependence signs. Saffron (Crocus sativus L.) stigma has been shown to have anxiolytic, antidepressant, and antinociceptive propertie...
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BDNF receptor antagonism during the induction of morphine Dependence exacerbates the severity of physical Dependence and ameliorates Psychological Dependence in rats.
Neuroscience letters, 2020Co-Authors: Fatemeh Rezamohammadi, Mehrnoush Rahmani, Ali Ghanbari, Ali Khaleghian, Hossein Miladi-gorjiAbstract:Abstract This study examined the effects of systemic administration of the TrkB receptor antagonist (ANA-12) during induction of morphine Dependence on the severity of physical and Psychological Dependence and the cerebrospinal fluid (CSF) BDNF levels in morphine-dependent and withdrawn rats. Rats became morphine-dependent by increasing daily doses of morphine for 7 days, along with ANA-12 injection. Then, rats were tested for the severity of physical Dependence on morphine (spontaneous withdrawal signs), anxiety-like (the elevated plus maze), depressive-like (sucrose preference test) behaviors after spontaneous morphine withdrawal. Also, the CSF BDNF levels were assessed 2 h after the last dose of morphine and day 13 after morphine withdrawal in morphine-dependent and withdrawn rats. We found that the morphine withdrawal signs were significantly higher in morphine dependent rats receiving ANA-12 on days of 5–7 after morphine withdrawal, also ANA-12 exacerbated overall Dependence severity. While, the percentage of time spent in the open arms and sucrose preference were higher in morphine-dependent rats receiving ANA-12 than morphine-dependent rats receiving saline. Also, the ANA-12 injection decreased the CSF BDNF levels following morphine Dependence, while increased it after morphine withdrawal. We conclude that the ANA-12 exacerbated the severity of physical morphine Dependence but attenuated the anxiety/depressive-like behaviors in morphine-dependent and withdrawn rats. Also, ANA-12 injection was able to reverse the changes in the CSF BDNF levels. Therefore, ANA-12 is not more likely to complete treatment for opiate addiction.
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Age- and sex-related changes in the severity of physical and Psychological Dependence in morphine-dependent rats.
Pharmacology biochemistry and behavior, 2019Co-Authors: Javad Mohammadian, Hossein Miladi-gorjiAbstract:Abstract Gender- and age-dependent effects on the severity of morphine Dependence are still controversial. The aim of this study was to investigate the effects of age and sex on the severity of physical and Psychological Dependence in morphine-dependent rats. The adult/aged male and female Wistar rats were chronically treated with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine for 14 days. Then, rats were tested for the severity of physical Dependence on morphine (spontaneous withdrawal signs), anxiety-like (the elevated plus maze), depressive-like (sucrose preference test) and grooming behaviors after spontaneous morphine withdrawal. We found that the morphine withdrawal signs decreased after 3 and 7 days of withdrawal in female and male rats respectively, while there was no significant difference in overall Dependence severity between the two sexes or ages. Also, we found that the withdrawal of morphine led to increased anxiety, depression and obsessive-compulsive behavior in the D (dependent)/Adult male and female rats. Also, the D/aged female and male rats exhibited a reduction in depressive-like behavior than the D/Adult rats. Moreover, the D/female rats exhibited a decreased obsessive-compulsive behavior in both age groups than male rats. We conclude that age has no effect on the duration of withdrawal from morphine and overall Dependence severity. While, the duration of withdrawal from morphine was lower in female than male rats. Our results showed a sex difference on the duration of morphine withdrawal and an age difference in the expression of Psychological Dependence on morphine. Thus, therapeutic strategies may be different for opiate-dependent individuals in physical and Psychological dimensions.
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Effects of BDNF receptor antagonist on the severity of physical and Psychological Dependence, morphine-induced locomotor sensitization and the ventral tegmental area-nucleus accumbens BDNF levels in morphine- dependent and withdrawn rats.
Neuroscience letters, 2017Co-Authors: Masoumeh Khalil-khalili, Ali Rashidy-pour, Ahmad Reza Bandegi, Behpoor Yousefi, Hassan Jorjani, Hossein Miladi-gorjiAbstract:Abstract This study examined the effects of systemic administration of the TrkB receptor antagonist (ANA-12) on the severity of physical and Psychological Dependence and morphine-induced locomotor sensitization, the ventral tegmental area (VTA)-nucleus accumbens (NAc) BDNF levels in morphine-dependent and withdrawn rats. Rats were injected with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine for 10 days. Then, rats were tested for naloxone-precipitated morphine withdrawal signs, the anxiety (the elevated plus maze-EPM) after the last morphine injection and injection of ANA12 (ip). Also, morphine-induced locomotor sensitization was evaluated after morphine challenge followed by an injection of ANA-12 in morphine-withdrawn rats. The VTA-NAc BDNF levels were assessed in morphine-dependent and withdrawn rats. The overall Gellert–Holtzman score was significantly higher in morphine-dependent rats receiving ANA-12 than in those receiving saline. Also, the percentage of time spent in the open arms in control and morphine-dependent rats receiving ANA-12 were higher compared to the Cont/Sal and D/Sal rats, respectively. There was no significant difference in the locomotor activity and the VTA-NAc BDNF levels between D/Sal/morphine and D/ANA-12/morphine groups after morphine withdrawal. We conclude that the systemic administration of ANA-12 exacerbates the severity of physical Dependence on morphine and partially attenuates the anxiety-like behavior in morphine-dependent rats. However, ANA-12 did not affect morphine-induced locomotor sensitization and the VTA-NAc BDNF levels in morphine-dependent and withdrawn rats.
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Effects of forced treadmill exercise during the induction of morphine Dependence on the severity of physical and Psychological Dependence in morphine-dependent rats
2017Co-Authors: Fatemeh Talebi-keyasari, Sakine Heidari, Moghadeseh Mehdinejad, Hossein Miladi-gorjiAbstract:Introduction: Previous studies have indicated that the voluntary and swimming exercise decreases the severity of the physical and Psychological Dependence on morphine in morphine-dependent and withdrawn rats. The aim of the present study was to investigate the effects of the forced treadmill exercise during the induction of morphine Dependence on naloxone-precipitated morphine withdrawal signs and anxiety like behavior. Materials and Methods: Rats were injected with increasing doses of morphine (8, 16, 26, 36, 46, 56 and 64 mg/kg, daily, s.c.) over a period of 7 days in which they were also trained at mild intensity on a treadmill for 30 min of daily. The anxiety-like behaviors were tested 2h after receiving morphine injection (56 mg/kg) using the elevated plus-maze (EPM) on day 8. Then, the severity of morphine Dependence was measured after an acute injection of naloxone (0.4mg/kg, IP), 2h after receiving morphine injection (56 mg/kg) according to a modified version of the Gellert–Holtzman scale on day 9. Results: The results showed that the withdrawal graded signs including abdominal contractions, weight loss, and overall Gellert–Holtzman score and among the checked signs; consisted of diarrhea, irritability and teach chattering were decreased in treadmill runner morphine-dependent rats than the sedentary rats. Also, the results showed that the treadmill runner morphine-dependent rats exhibited an increase in time spent in, and entries into, the EPM open arms than the sedentary morphine-dependent groups. Conclusion: Our findings indicated that the forced treadmill exercise during the induction of morphine Dependence diminished the severity of Dependence on morphine and anxiety like behavior. Thus, forced treadmill exercise may decrease some of the behavioral consequences of physical and Psychological Dependence on morphine. Keywords: Morphine Dependence, Forced treadmill exercise, Anxiety, Rats
Guodong Gao - One of the best experts on this subject based on the ideXlab platform.
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Stereotactic Neurosurgery for Drug Addiction
Neurosurgical Treatments for Psychiatric Disorders, 2014Co-Authors: Guodong Gao, Xuelian WangAbstract:Drug addiction is also known as drug Dependence. A committee of experts from WHO defined drug addiction as a mental, and sometimes a physical, state caused by the interaction of the drug with the organism. Individuals addicted to a drug exhibit a compulsive and continuous drug-taking behavior along with other reactions. The aim of these reactions is either to experience euphoria or to avoid the discomfort caused by drug withdrawal. The core feature of addiction is that the addicts know that the behavior is pernicious but they cannot control their intake. Drug addiction includes two parts, physiological Dependence (physical Dependence) and Psychological Dependence (psychic Dependence). Physiological Dependence is a physiological adaptation state caused by repeated drug consumption and displays drug tolerance and withdrawal syndrome. Psychological Dependence is the euphoria caused by drug consumption and underlies the need for continuous consumption to experience the euphoria repeatedly. It is the main cause for relapse into drug addiction.
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Preliminary findings in ablating the nucleus accumbens using stereotactic surgery for alleviating Psychological Dependence on alcohol
Neuroscience letters, 2010Co-Authors: Xuelian Wang, Chongwang Chang, Li Gao, Ning Geng, Wei Zhao, Guodong GaoAbstract:Abstract We studied the effect of stereotactic surgery in cases of alcohol Dependence. Twelve patients with a Psychological Dependence on alcohol (treated systematically with medication for detoxification 3–8 times in various rehabilitation centers before, but had relapsed within 2 weeks after withdrawal) were treated by ablating the nucleus accumbens (NA C ) bilaterally using stereotactic surgery. The therapeutic effect and safety evaluation index of the surgery were analyzed. The timing of the conducted evaluations was preoperatively and in the sixth postoperative month. Currently, relapse has not occurred in 9 cases. Relapse occurred in 3 cases after surgery. The prevalence of relapse was 16.7% within 6 months, and 25% within 12 months. Non-specific complications of this type of surgery (e.g., intracranial hematoma, infection) were not observed. One case in 12 patients suffered dysosmia, but he recovered completely 4 months later after surgery. The full-scale intelligence quotient (FSIQ) and memory quotient (MQ) of these patients were significantly improved 6 months postoperatively compared with preoperatively. The severity of alcohol Dependence scale and a scale measuring alcohol craving in these patients were significantly decreased. There were also significant changes over time in the Minnesota multiphasic personality inventory (MMPI) profile, suggesting a decrease in depression, irritability, and psychopathy. Ablating specified targets (NA C ) using stereotactic surgery is a safe method to alleviate alcohol craving, reduce relapse rates and improve quality-of-life in patients with Psychological Dependence on alcohol.
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clinical study for alleviating opiate drug Psychological Dependence by a method of ablating the nucleus accumbens with stereotactic surgery
Stereotactic and Functional Neurosurgery, 2003Co-Authors: Guodong Gao, Xuelian Wang, Qingfeng Wang, Qinchuan Liang, Yaqun Zhao, Fang Hou, Ling ChenAbstract:The aim of this study was to explore a new way of treating drug addiction by ablating the nucleus accumbens (NAC), which has a close relationship with drug-induced Psychological Dependence,
Seitaro Ohkuma - One of the best experts on this subject based on the ideXlab platform.
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upregulation of l type cav1 channels in the development of Psychological Dependence
Synapse, 2010Co-Authors: Masahiro Shibasaki, Kazuhiro Kurokawa, Seitaro OhkumaAbstract:Although L-type voltage-dependent Ca2+ channels regulate activity-dependent processes including synaptic plasticity and synapse formation, there are few data on the changes of Cav1 channel expression in Psychological Dependence. This study investigated the role of L-type Cav1 channel expression in the brain of mouse that was Psychologically dependent on methamphetamine (2 mg/kg, subcutaneous injection [s.c.]), cocaine (10 mg/kg, s.c.), and morphine (5 mg/kg, s.c.) with the conditioned place preference paradigm. Intracerebroventricular administration of nifedipine (3, 10, and 30 nmol/mouse) dose-dependently reduced the development of methamphetamine-, cocaine-, and morphine-induced rewarding effect. Under such conditions, protein levels of both Cav1.2 and Cav1.3 in the frontal cortex and the limbic forebrain were significantly increased on methamphetamine-, cocaine-, and morphine-induced Psychologically dependent mice. These findings suggest that the upregulation of Cav1.2 and Cav1.3 participated in the development of Psychological Dependence. Synapse 64:440–444, 2010. © 2010 Wiley-Liss, Inc.
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Upregulation of L‐type Cav1 channels in the development of Psychological Dependence
Synapse (New York N.Y.), 2010Co-Authors: Masahiro Shibasaki, Kazuhiro Kurokawa, Seitaro OhkumaAbstract:Although L-type voltage-dependent Ca2+ channels regulate activity-dependent processes including synaptic plasticity and synapse formation, there are few data on the changes of Cav1 channel expression in Psychological Dependence. This study investigated the role of L-type Cav1 channel expression in the brain of mouse that was Psychologically dependent on methamphetamine (2 mg/kg, subcutaneous injection [s.c.]), cocaine (10 mg/kg, s.c.), and morphine (5 mg/kg, s.c.) with the conditioned place preference paradigm. Intracerebroventricular administration of nifedipine (3, 10, and 30 nmol/mouse) dose-dependently reduced the development of methamphetamine-, cocaine-, and morphine-induced rewarding effect. Under such conditions, protein levels of both Cav1.2 and Cav1.3 in the frontal cortex and the limbic forebrain were significantly increased on methamphetamine-, cocaine-, and morphine-induced Psychologically dependent mice. These findings suggest that the upregulation of Cav1.2 and Cav1.3 participated in the development of Psychological Dependence. Synapse 64:440–444, 2010. © 2010 Wiley-Liss, Inc.
Tsutomu Suzuki - One of the best experts on this subject based on the ideXlab platform.
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The K + -Cl − Cotransporter KCC2 and Zolpidem
Neuropathology of Drug Addictions and Substance Misuse, 2016Co-Authors: Masahiro Shibasaki, Tomohisa Mori, Tsutomu SuzukiAbstract:Zolpidem is a short-acting nonbenzodiazepine that is prescribed to treat insomnia, and it also induces Psychological Dependence. Zolpidem binds to the benzodiazepine binding site that is located on the GABA A receptor, and activation of the GABA A receptor by GABA results in an increase in Cl − influx. Cl − homeostasis in neurons is also modulated by KCC2, which can regulate Cl − efflux to equilibrate the membrane potential in mature neurons. Thus, it is possible that continuous Cl − influx via stimulation of the GABA A receptor may also affect the efflux of Cl − as KCC2 in Cl − homeostasis. In this chapter we will describe the role of KCC2 in Psychological Dependence by chronic treatment with zolpidem.
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Glutamatergic neurotransmission and protein kinase C play a role in neuron-glia communication during the development of methamphetamine-induced Psychological Dependence.
The European journal of neuroscience, 2005Co-Authors: Mayumi Miyatake, Masahiro Shibasaki, Minoru Narita, Atsushi Nakamura, Tsutomu SuzukiAbstract:Methamphetamine (METH) is a strongly addictive psychostimulant that dramatically affects the central nervous system (CNS). On the other hand, protein kinase C (PKC) plays a major role in cellular regulatory and signalling processes that involve protein phosphorylation. The purpose of this study was to investigate the role of neuronal and astrocytic PKC in changes in the central glutamatergic system induced by METH. We show here that in vitro treatment with METH caused the phosphorylation of both neuronal and astrocytic PKC and the activation of astrocytes in cortical neuron/glia co-cultures. Treatment of cortical neuron/glia co-cultures with either the PKC activator phorbol 12,13-dibutyrate (PDBu) or glutamate also caused the PKC-dependent activation of astrocytes. The PKC inhibitor chelerythrine suppressed the Ca2+ responses to glutamate in both cortical neurons and astrocytes. Moreover, a low concentration of PDBu significantly enhanced the Ca2+ responses to glutamate, but not to dopamine, in both cortical neurons and astrocytes. Notably, treatment with METH also enhanced the Ca2+ responses to glutamate in cortical neurons. The activation of astrocytes induced by METH was also reversed by co-treatment with glutamate receptor antagonists (ifenprodil, DNQX or MPEP) in cortical neuron/glia co-cultures. In the conditioned place preference paradigm, intracerebroventricular administration of glutamate receptor antagonists (ifenprodil, DNQX or MPEP) attenuated the METH-induced rewarding effect. These findings provide evidence that the changes in PKC-dependent neuronal and astrocytic glutamatergic transmission induced by METH may, at least in part, contribute to the development of Psychological Dependence on METH.
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Treatment for Psychological Dependence on morphine: usefulness of inhibiting NMDA receptor and its associated protein kinase in the nucleus accumbens.
Life sciences, 2005Co-Authors: Minoru Narita, Yoshinori Yajima, Hideaki Kato, Kan Miyoshi, Takeshi Aoki, Tsutomu SuzukiAbstract:A growing body of evidence indicates that the mesolimbic dopaminergic (DAergic) pathway projecting from the ventral tegmental area (VTA) to the nucleus accumbens (N.Acc.) play a critical role in the initiation of Psychological Dependence on morphine. As well as DAergic system, the involvement of non-DAergic neurotransmitter and neuromodulator systems in rewarding effects induced by morphine has been recently documented. We previously demonstrated that the morphine-induced rewarding effect was dramatically suppressed by co-treatment with NMDA receptor antagonists, such as dizocilpine (MK-801), ketamine and ifenprodil. Therefore, we propose here that inhibiting the N-methyl-D-aspartate (NMDA) receptor and its associated protein kinase in the N.Acc. is useful for the treatment for Psychological Dependence on morphine. The following review provides a summary of recent our findings regarding the role of NMDA receptor and its associated protein kinase in the development of Psychological Dependence on morphine.
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Implication of cyclin-dependent kinase 5 in the development of Psychological Dependence on and behavioral sensitization to morphine
Journal of Neurochemistry, 2005Co-Authors: Minoru Narita, Yasuyuki Nagumo, Masahiro Shibasaki, Michiko Narita, Yoshinori Yajima, Tsutomu SuzukiAbstract:In the present study, we investigated the role of cyclin-dependent kinase 5 (cdk5) in the brain dynamics changed by repeated in vivo treatment with morphine. The level of phosphorylated-cdk5 was significantly increased in the cingulate cortex of mice showing the morphine-induced rewarding effect. Under these conditions, roscovitine, a cdk5 inhibitor, given intracerebroventricularly (i.c.v.) caused a dose-dependent and significant inhibition of the morphine-induced rewarding effect. In addition, the dose–response effect of the morphine-induced rewarding effect was dramatically attenuated in cdk5 heterozygous (+/–) knockout mice. Furthermore, the development of behavioral sensitization by intermittent administration of morphine was virtually abolished in cdk5 (+/–) mice. These findings suggest that the induction and/or activation of cdk5 are implicated in the development of Psychological Dependence on morphine.
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Basic studies on cancer pain control
Gan to kagaku ryoho. Cancer & chemotherapy, 2005Co-Authors: Yoshinori Yajima, Minoru Narita, Masahiko Ozaki, Keiichi Niikura, Tsutomu SuzukiAbstract:According to the World Health Organization (WHO) guidelines for patients with moderate or severe pain, morphine has been used as a "gold standard" treatment for cancer pain. Recent clinical experiences have demonstrated that when morphine is used to control pain in cancer patients, Psychological Dependence is not a major concern. However, undue anxiety about Psychological Dependence on morphine in cancer patients has caused physicians and patients to use inadequate doses of opioids. In basic research, we reported that the morphine-induced rewarding effects can be dramatically suppressed under a neuropathic pain-like state induced by sciatic nerve ligation and an inflammatory pain-like state produced by intraplantar injection of formalin or carrageenan in rodents. The use of morphine for the treatment of pain is sometimes accompanied with side effects such as emesis, constipation and drowsiness. We show that the lower doses of morphine produce emesis, whereas antinociceptive doses of morphine show no emetic responses in ferrets. These findings provide further evidence that an adequate dose of morphine is useful and safe in a clinical setting.