The Experts below are selected from a list of 138 Experts worldwide ranked by ideXlab platform
Hackseang Kim - One of the best experts on this subject based on the ideXlab platform.
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inhibition of muscimol on morphine induced hyperactivity Reverse Tolerance and postsynaptic dopamine receptor supersensitivity
Pharmacology, 2002Co-Authors: Inseup Yoon, Hackseang Kim, Jintae Hong, Myung Koo LeeAbstract:This study was performed to investigate the effect of muscimol on morphine-induced hyperactivity, Reverse Tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration
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inhibition of baclofen on morphine induced hyperactivity Reverse Tolerance and postsynaptic dopamine receptor supersensitivity
Pharmacological Research, 2001Co-Authors: Sanghee Woo, Hackseang Kim, Jaesuk Yun, Myung Koo Lee, Yeonhee Seong, Choongon JangAbstract:This study was performed to investigate the effect of tetrahydroisoxazolopyridine (THIP), a GABAA agonist, on the morphine-induced hyperactivity, Reverse Tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity in mice. However, the morphine-induced hyperactivity was inhibited dose-dependently by the administration of THIP (0.2, 0.4 and 0.8 mg/kg, i.p.). In contrast, daily administration of morphine resulted in a Reverse Tolerance to the hyperactivity caused by morphine (10 mg/kg, s.c). THIP inhibited the development of Reverse Tolerance in the mice that had received the repeated same morphine (10 mg/kg, s.c.) doses. The postsynaptic dopamine receptor supersensitivity, which was evidenced by the enhanced ambulatory activity after the administration of apomorphine (2 mg/kg, s.c), also developed in the Reverse tolerant mice. THIP also inhibited the development of the postsynaptic dopamine receptor supersensitivity induced by the chronic morphine administration. These results suggest that the hyperactivity, Reverse Tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine can be inhibited activating the GABAA receptors.
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inhibition of baclofen on morphine induced hyperactivity Reverse Tolerance and postsynaptic dopamine receptor supersensitivity
Pharmacological Research, 2001Co-Authors: Sanghee Woo, Hackseang Kim, Jaesuk Yun, Myung Koo Lee, Yeonhee Seong, Choongon JangAbstract:Abstract The effects of baclofen on the development of Reverse Tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine were examined in mice. A single administration of morphine induced hyperactivity and the morphine-induced hyperactivity was inhibited dose dependently by the administration of a GABA B receptor agonist, baclofen (1.25, 2.5 and 5 mg kg −1 , i.p.). Daily repeated administration of morphine developed Reverse Tolerance to the hyperactivity of morphine. The concomitant administration of baclofen inhibited the morphine-induced hyperactivity and the baclofen administration prior to and during the chronic administration of morphine in mice inhibited the development of Reverse Tolerance to the hyperactivity of morphine (10 mg kg −1 , s.c.). Postsynaptic dopamine receptor supersensitivity was also developed in Reverse-tolerant mice that had received the same morphine. The development of postsynaptic dopamine receptor supersensitivity was evidenced by the enhanced ambulatory activity of apomorphine (2 mg kg −1 , s.c.). Baclofen also inhibited the development of postsynaptic dopamine receptor supersensitivity induced by the chronic administration of morphine. These results suggest that the hyperactivity, Reverse Tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine may be modulated via the activation of GABA B receptors induced by baclofen.
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inhibitory effects of ginseng total saponin on nicotine induced hyperactivity Reverse Tolerance and dopamine receptor supersensitivity
Behavioural Brain Research, 1999Co-Authors: Hackseang Kim, Kilsoon KimAbstract:A single administration of a low dose of nicotine produced hyperactivity in mice. A repeated administration of nicotine developed Reverse Tolerance to the ambulation-accelerating activity of nicotine and also developed postsynaptic dopamine (DA) receptor supersensitivity. The development of Reverse Tolerance was evidenced by an increased ambulatory response to nicotine, and the development of postsynaptic DA receptor supersensitivity was evidenced by the enhanced response in ambulatory activity to apomorphine, a DA receptor agonist. Administration of ginseng total saponin (GTS) prior to and during the nicotine treatment in mice inhibited not only nicotine-induced hyperactivity and Reverse Tolerance, but also postsynaptic DA receptor supersensitivity in nicotine-induced Reverse tolerant mice. These results suggest that inhibition by GTS of nicotine-induced hyperactivity and Reverse Tolerance may be closely related with the inhibition of the dopaminergic activation induced by nicotine and that the development of nicotine-induced Reverse Tolerance may be associated with enhanced DA receptor sensitivity.
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antinarcotic effects of the velvet antler water extract on morphine in mice
Journal of Ethnopharmacology, 1999Co-Authors: Hackseang Kim, Hwakyung Lim, Wookyu ParkAbstract:The present study was undertaken to investigate the antinarcotic effects of velvet antler water extract (VAWE) from Cervus elaphus on morphine. Morphine-induced analgesic action was measured by tail-flick method. Morphine-induced hyperactivity and Reverse Tolerance were evidenced by measuring the enhanced ambulatory activity using a tilting-type ambulometer. Dopamine (DA) receptor supersensitivity in mice displaying morphine-induced Reverse Tolerance was evidenced by the enhanced response in ambulatory activity to the DA agonist, apomorphine. The repeated administration of VAWE significantly inhibits the development of morphine-induced analgesic Tolerance, physical dependence, Reverse Tolerance and postsynaptic DA receptor supersensitivity. But a single administration of VAWE did neither antagonize morphine-induced analgesia nor inhibit morphine-induced hyperactivity. From the above results, it is presumed that VAWE may be useful for prevention and therapy of the adverse actions of morphine caused by the repeated administration of morphine.
Graeme Henderson - One of the best experts on this subject based on the ideXlab platform.
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effect of tamoxifen and brain penetrant protein kinase c and c jun n terminal kinase inhibitors on Tolerance to opioid induced respiratory depression in mice
Journal of Pharmacology and Experimental Therapeutics, 2017Co-Authors: Sarah L Withey, William L Dewey, Rob Hill, Abigail Lyndon, Eamonn Kelly, Graeme HendersonAbstract:Respiratory depression is the major cause of death in opioid overdose. We have previously shown that prolonged treatment of mice with morphine induces profound Tolerance to the respiratory depressant effects of the drug (Hill et al., 2016, Neuropsychopharmacol 41:762-773). The aim of the present study was to investigate whether Tolerance to opioid-induced respiratory depression is mediated by protein kinase C (PKC) and/or c-Jun N-terminal kinase (JNK). We found that whilst mice treated for up to six days with morphine developed Tolerance, as measured by the reduced responsiveness to an acute challenge dose of morphine, administration of the brain-penetrant PKC inhibitors tamoxifen and calphostin C, restored the ability of acute morphine to produce respiratory depression in morphine-treated mice. Importantly reversal of opioid Tolerance was dependent on the nature of the opioid ligand used to induce Tolerance, as these PKC inhibitors did not Reverse Tolerance induced by prolonged treatment of mice with methadone nor did they Reverse the protection to acute morphine-induced respiratory depression afforded by prolonged treatment with buprenorphine. We found no evidence for the involvement of JNK in morphine-induced Tolerance to respiratory depression. These results indicate that PKC represents a major mechanism underlying morphine Tolerance, that the mechanism of opioid Tolerance to respiratory depression is ligand-dependent, and that co-administration of drugs with PKC-inhibitory activity and morphine (as well as heroin, largely metabolized to morphine in the body) may render individuals more susceptible to overdose death by reversing Tolerance to the effects of morphine.
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effect of tamoxifen and brain penetrant protein kinase c and c jun n terminal kinase inhibitors on Tolerance to opioid induced respiratory depression in mice
Journal of Pharmacology and Experimental Therapeutics, 2017Co-Authors: Sarah L Withey, William L Dewey, Rob Hill, Abigail Lyndon, Eamonn Kelly, Graeme HendersonAbstract:Respiratory depression is the major cause of death in opioid overdose. We have previously shown that prolonged treatment of mice with morphine induces profound Tolerance to the respiratory-depressant effects of the drug (Hill et al., 2016). The aim of the present study was to investigate whether Tolerance to opioid-induced respiratory depression is mediated by protein kinase C (PKC) and/or c-Jun N-terminal kinase (JNK). We found that although mice treated for up to 6 days with morphine developed Tolerance, as measured by the reduced responsiveness to an acute challenge dose of morphine, administration of the brain-penetrant PKC inhibitors tamoxifen and calphostin C restored the ability of acute morphine to produce respiratory depression in morphine-treated mice. Importantly, reversal of opioid Tolerance was dependent on the nature of the opioid ligand used to induce Tolerance, as these PKC inhibitors did not Reverse Tolerance induced by prolonged treatment of mice with methadone nor did they Reverse the protection to acute morphine-induced respiratory depression afforded by prolonged treatment with buprenorphine. We found no evidence for the involvement of JNK in morphine-induced Tolerance to respiratory depression. These results indicate that PKC represents a major mechanism underlying morphine Tolerance, that the mechanism of opioid Tolerance to respiratory depression is ligand-dependent, and that coadministration of drugs with PKC-inhibitory activity and morphine (as well as heroin, largely metabolized to morphine in the body) may render individuals more susceptible to overdose death by reversing Tolerance to the effects of morphine.
William L Dewey - One of the best experts on this subject based on the ideXlab platform.
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effect of tamoxifen and brain penetrant protein kinase c and c jun n terminal kinase inhibitors on Tolerance to opioid induced respiratory depression in mice
Journal of Pharmacology and Experimental Therapeutics, 2017Co-Authors: Sarah L Withey, William L Dewey, Rob Hill, Abigail Lyndon, Eamonn Kelly, Graeme HendersonAbstract:Respiratory depression is the major cause of death in opioid overdose. We have previously shown that prolonged treatment of mice with morphine induces profound Tolerance to the respiratory depressant effects of the drug (Hill et al., 2016, Neuropsychopharmacol 41:762-773). The aim of the present study was to investigate whether Tolerance to opioid-induced respiratory depression is mediated by protein kinase C (PKC) and/or c-Jun N-terminal kinase (JNK). We found that whilst mice treated for up to six days with morphine developed Tolerance, as measured by the reduced responsiveness to an acute challenge dose of morphine, administration of the brain-penetrant PKC inhibitors tamoxifen and calphostin C, restored the ability of acute morphine to produce respiratory depression in morphine-treated mice. Importantly reversal of opioid Tolerance was dependent on the nature of the opioid ligand used to induce Tolerance, as these PKC inhibitors did not Reverse Tolerance induced by prolonged treatment of mice with methadone nor did they Reverse the protection to acute morphine-induced respiratory depression afforded by prolonged treatment with buprenorphine. We found no evidence for the involvement of JNK in morphine-induced Tolerance to respiratory depression. These results indicate that PKC represents a major mechanism underlying morphine Tolerance, that the mechanism of opioid Tolerance to respiratory depression is ligand-dependent, and that co-administration of drugs with PKC-inhibitory activity and morphine (as well as heroin, largely metabolized to morphine in the body) may render individuals more susceptible to overdose death by reversing Tolerance to the effects of morphine.
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effect of tamoxifen and brain penetrant protein kinase c and c jun n terminal kinase inhibitors on Tolerance to opioid induced respiratory depression in mice
Journal of Pharmacology and Experimental Therapeutics, 2017Co-Authors: Sarah L Withey, William L Dewey, Rob Hill, Abigail Lyndon, Eamonn Kelly, Graeme HendersonAbstract:Respiratory depression is the major cause of death in opioid overdose. We have previously shown that prolonged treatment of mice with morphine induces profound Tolerance to the respiratory-depressant effects of the drug (Hill et al., 2016). The aim of the present study was to investigate whether Tolerance to opioid-induced respiratory depression is mediated by protein kinase C (PKC) and/or c-Jun N-terminal kinase (JNK). We found that although mice treated for up to 6 days with morphine developed Tolerance, as measured by the reduced responsiveness to an acute challenge dose of morphine, administration of the brain-penetrant PKC inhibitors tamoxifen and calphostin C restored the ability of acute morphine to produce respiratory depression in morphine-treated mice. Importantly, reversal of opioid Tolerance was dependent on the nature of the opioid ligand used to induce Tolerance, as these PKC inhibitors did not Reverse Tolerance induced by prolonged treatment of mice with methadone nor did they Reverse the protection to acute morphine-induced respiratory depression afforded by prolonged treatment with buprenorphine. We found no evidence for the involvement of JNK in morphine-induced Tolerance to respiratory depression. These results indicate that PKC represents a major mechanism underlying morphine Tolerance, that the mechanism of opioid Tolerance to respiratory depression is ligand-dependent, and that coadministration of drugs with PKC-inhibitory activity and morphine (as well as heroin, largely metabolized to morphine in the body) may render individuals more susceptible to overdose death by reversing Tolerance to the effects of morphine.
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determination of the role of conventional novel and atypical pkc isoforms in the expression of morphine Tolerance in mice
Pain, 2007Co-Authors: Forrest L Smith, Paul A Smith, Bichoy H Gabra, Marcia C Redwood, William L DeweyAbstract:Abstract This study comprehensively determines the role of all the major PKC isoforms in the expression morphine Tolerance. Pseudosubstrate and receptors for activated C-kinase (RACK) peptides inhibit only a single PKC isoform, while previously tested chemical PKC inhibitors simultaneously inhibit multiple isoforms making it impossible to determine which PKC isoform mediates morphine Tolerance. Tolerance can result in a diminished effect during continued exposure to the same amount of substance. In rodents, morphine pellets provide sustained exposures to morphine leading to the development of Tolerance by 72 h. We hypothesized that administration of the PKC isoform inhibitors i.c.v. would Reverse Tolerance and reinstate antinociception in the tail immersion and hot plate tests from the morphine released solely from the pellet. Inhibitors to PKCα, γ and e (100–625 pmol) dose-dependently reinstated antinociception in both tests. The PKCβI, βII, δ, θ, e, η and ξ inhibitors were inactive (up to 2500 pmol). In other mice, the degree of morphine Tolerance was determined by calculating ED50 and potency-ratio values following s.c. morphine administration. Morphine s.c. was 5.6-fold less potent in morphine-pelleted vs. placebo-pelleted mice. Co-administration of s.c. morphine with the inhibitors i.c.v. to either PKCα (625 pmol), γ (100 pmol) or e (400 pmol) completely Reversed the Tolerance so that s.c. morphine was equally potent in both placebo- and morphine-pelleted mice. The PKCβI, βII, δ, θ, e, η and ξ inhibitors were inactive. Thus, PKCα, γ and e appear to contribute to the expression of morphine Tolerance in mice.
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pkc and pka inhibitors Reverse Tolerance to morphine induced hypothermia and supraspinal analgesia in mice
European Journal of Pharmacology, 2004Co-Authors: Ruby R Javed, William L Dewey, Paul A Smith, Forrest L SmithAbstract:Morphine antinociceptive Tolerance in the tail-flick test is completely Reversed by inhibitors of protein kinase C (PKC) or cAMP-dependent protein kinase (PKA). The effects of these inhibitors on Tolerance to supraspinally mediated antinociception, such as the hot-plate test was unknown, as well as their effects in tests of mechanical nociception. The PKC inhibitors bisinolylmaleimide I ((2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide) and Go-7874 {2[1[(3-Dimethylaminopropyl)-5-methozyindol-3-yl]-3-(1H-indol-3-yl) hydrochloride} completely Reversed the Tolerance to morphine in both the hot-plate and tail-pinch tests. Similarly, the PKA inhibitor KT-5720 (8R, 9S, 11S)-(−)-9-hydroxy-9-hexoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo[a,g]cycloocta[cde]trinden-1-one also Reversed Tolerance in both tests. The role of PKC and PKA in mediating Tolerance to morphine-induced hypothermia was also investigated. Bisinolylmaleimide I, Go-7874 and KT-5720 only partly Reversed the 32-fold level of Tolerance induced by the morphine pellets. However, co-administration of bisinolylmaleimide I with KT-5720 or Go-7874 with KT-5720 completely Reversed the Tolerance. This demonstrates that Tolerance in a non-behavioral system involves the actions of PKC and PKA.
Choongon Jang - One of the best experts on this subject based on the ideXlab platform.
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inhibition of baclofen on morphine induced hyperactivity Reverse Tolerance and postsynaptic dopamine receptor supersensitivity
Pharmacological Research, 2001Co-Authors: Sanghee Woo, Hackseang Kim, Jaesuk Yun, Myung Koo Lee, Yeonhee Seong, Choongon JangAbstract:This study was performed to investigate the effect of tetrahydroisoxazolopyridine (THIP), a GABAA agonist, on the morphine-induced hyperactivity, Reverse Tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity in mice. However, the morphine-induced hyperactivity was inhibited dose-dependently by the administration of THIP (0.2, 0.4 and 0.8 mg/kg, i.p.). In contrast, daily administration of morphine resulted in a Reverse Tolerance to the hyperactivity caused by morphine (10 mg/kg, s.c). THIP inhibited the development of Reverse Tolerance in the mice that had received the repeated same morphine (10 mg/kg, s.c.) doses. The postsynaptic dopamine receptor supersensitivity, which was evidenced by the enhanced ambulatory activity after the administration of apomorphine (2 mg/kg, s.c), also developed in the Reverse tolerant mice. THIP also inhibited the development of the postsynaptic dopamine receptor supersensitivity induced by the chronic morphine administration. These results suggest that the hyperactivity, Reverse Tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine can be inhibited activating the GABAA receptors.
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inhibition of baclofen on morphine induced hyperactivity Reverse Tolerance and postsynaptic dopamine receptor supersensitivity
Pharmacological Research, 2001Co-Authors: Sanghee Woo, Hackseang Kim, Jaesuk Yun, Myung Koo Lee, Yeonhee Seong, Choongon JangAbstract:Abstract The effects of baclofen on the development of Reverse Tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine were examined in mice. A single administration of morphine induced hyperactivity and the morphine-induced hyperactivity was inhibited dose dependently by the administration of a GABA B receptor agonist, baclofen (1.25, 2.5 and 5 mg kg −1 , i.p.). Daily repeated administration of morphine developed Reverse Tolerance to the hyperactivity of morphine. The concomitant administration of baclofen inhibited the morphine-induced hyperactivity and the baclofen administration prior to and during the chronic administration of morphine in mice inhibited the development of Reverse Tolerance to the hyperactivity of morphine (10 mg kg −1 , s.c.). Postsynaptic dopamine receptor supersensitivity was also developed in Reverse-tolerant mice that had received the same morphine. The development of postsynaptic dopamine receptor supersensitivity was evidenced by the enhanced ambulatory activity of apomorphine (2 mg kg −1 , s.c.). Baclofen also inhibited the development of postsynaptic dopamine receptor supersensitivity induced by the chronic administration of morphine. These results suggest that the hyperactivity, Reverse Tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine may be modulated via the activation of GABA B receptors induced by baclofen.
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blockade by naloxone of cocaine induced hyperactivity Reverse Tolerance and conditioned place preference in mice
Behavioural Brain Research, 1997Co-Authors: Hackseang Kim, Wookyu Park, Choongon Jang, Jaeyang Kong, Hangmook Rheu, Daehyun Cho, Seogyoun KangAbstract:Cocaine-induced hyperactivity was inhibited by a single administration of naloxone (2 and 5 mg/kg, i.p.), an opioid receptor antagonist, and naloxone administered prior to and during the chronic injection of cocaine attenuated the development of both cocaine-induced Reverse Tolerance and conditioned place preference (CPP). Dopamine (DA) receptor supersensitivity which developed in cocaine-induced Reverse tolerant or CPP mice, was also inhibited by naloxone. Furthermore, naloxone reduced an apomorphine-induced striatal dopaminergic action, climbing behavior. Therefore, the present studies suggest that cocaine-induced dopaminergic behaviors, such as hyperactivity, Reverse Tolerance and CPP, may be commonly produced via activation of an opioid receptor. The development of DA receptor supersensitivity may be a possible common mechanism of cocaine-induced Reverse Tolerance and CPP, since cocaine-induced changes in sensitivity to apomorphine, as well as apomorphine-induced climbing behavior in mice, were both inhibited by naloxone.
Myung Koo Lee - One of the best experts on this subject based on the ideXlab platform.
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inhibition of muscimol on morphine induced hyperactivity Reverse Tolerance and postsynaptic dopamine receptor supersensitivity
Pharmacology, 2002Co-Authors: Inseup Yoon, Hackseang Kim, Jintae Hong, Myung Koo LeeAbstract:This study was performed to investigate the effect of muscimol on morphine-induced hyperactivity, Reverse Tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration
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inhibition of thip on morphine induced hyperactivity Reverse Tolerance and postsynaptic dopamine receptor supersensitivity
Archives of Pharmacal Research, 2002Co-Authors: Inseup Yoon, Imchul Shin, Jintae Hong, Myung Koo LeeAbstract:This study was performed to investigate the effect of tetrahydroisoxazolopyridine (THIP), a GABAA agonist, on the morphine-induced hyperactivity, Reverse Tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity in mice. However, the morphine-induced hyperactivity was inhibited dose-dependently by the administration of THIP (0.2, 0.4 and 0.8 mg/kg, i.p.). In contrast, daily administration of morphine resulted in a Reverse Tolerance to the hyperactivity caused by morphine (10 mg/kg, s.c.). THIP inhibited the development of Reverse Tolerance in the mice that had received the repeated same morphine (10 mg/kg, s.c.) doses. The postsynaptic dopamine receptor super-sensitivity, which was evidenced by the enhanced ambulatory activity after the administration of apomorphine (2 mg/kg, s.c.), also developed in the Reverse tolerant mice. THIP also inhibited the development of the postsynaptic dopamine receptor supersensitivity induced by the chronic morphine administration. These results suggest that the hyperactivity, Reverse Tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine can be inhibited activating the GABAA receptors.
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inhibition of baclofen on morphine induced hyperactivity Reverse Tolerance and postsynaptic dopamine receptor supersensitivity
Pharmacological Research, 2001Co-Authors: Sanghee Woo, Hackseang Kim, Jaesuk Yun, Myung Koo Lee, Yeonhee Seong, Choongon JangAbstract:This study was performed to investigate the effect of tetrahydroisoxazolopyridine (THIP), a GABAA agonist, on the morphine-induced hyperactivity, Reverse Tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity in mice. However, the morphine-induced hyperactivity was inhibited dose-dependently by the administration of THIP (0.2, 0.4 and 0.8 mg/kg, i.p.). In contrast, daily administration of morphine resulted in a Reverse Tolerance to the hyperactivity caused by morphine (10 mg/kg, s.c). THIP inhibited the development of Reverse Tolerance in the mice that had received the repeated same morphine (10 mg/kg, s.c.) doses. The postsynaptic dopamine receptor supersensitivity, which was evidenced by the enhanced ambulatory activity after the administration of apomorphine (2 mg/kg, s.c), also developed in the Reverse tolerant mice. THIP also inhibited the development of the postsynaptic dopamine receptor supersensitivity induced by the chronic morphine administration. These results suggest that the hyperactivity, Reverse Tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine can be inhibited activating the GABAA receptors.
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inhibition of baclofen on morphine induced hyperactivity Reverse Tolerance and postsynaptic dopamine receptor supersensitivity
Pharmacological Research, 2001Co-Authors: Sanghee Woo, Hackseang Kim, Jaesuk Yun, Myung Koo Lee, Yeonhee Seong, Choongon JangAbstract:Abstract The effects of baclofen on the development of Reverse Tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine were examined in mice. A single administration of morphine induced hyperactivity and the morphine-induced hyperactivity was inhibited dose dependently by the administration of a GABA B receptor agonist, baclofen (1.25, 2.5 and 5 mg kg −1 , i.p.). Daily repeated administration of morphine developed Reverse Tolerance to the hyperactivity of morphine. The concomitant administration of baclofen inhibited the morphine-induced hyperactivity and the baclofen administration prior to and during the chronic administration of morphine in mice inhibited the development of Reverse Tolerance to the hyperactivity of morphine (10 mg kg −1 , s.c.). Postsynaptic dopamine receptor supersensitivity was also developed in Reverse-tolerant mice that had received the same morphine. The development of postsynaptic dopamine receptor supersensitivity was evidenced by the enhanced ambulatory activity of apomorphine (2 mg kg −1 , s.c.). Baclofen also inhibited the development of postsynaptic dopamine receptor supersensitivity induced by the chronic administration of morphine. These results suggest that the hyperactivity, Reverse Tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine may be modulated via the activation of GABA B receptors induced by baclofen.
