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R. Webb - One of the best experts on this subject based on the ideXlab platform.
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Extra- and intracellular effects of divergent selection for pituitary responsiveness to gonadotropin-releasing hormone in prepubertal ram lambs.
Biology of reproduction, 1997Co-Authors: N. P. Evans, J R Mcneilly, T. A. Bramley, R. WebbAbstract:Divergent selection based on the response of 10-wk-old male lambs to a GnRH challenge has produced two Lines of sheep, referred to as high and low Lines, that differ in their ability to release LH in response to pharmacological and physiological doses of GnRH. The aim of this study was to determine whether the between-Line Differences in pituitary sensitivity were related to Differences in GnRH receptor number and/or the transduction of the intracellular signal following GnRH receptor activation. Pituitary glands were collected from fourteen 20-wk-old ram lambs from each Line, weighed, and sampled for GnRH receptor analysis. The remaining tissue from 9 lambs from each Line was dispersed. Of the resultant cell suspension, a sample was stored for measurement of GnRH receptor content and the remainder was plated and cultured for 24 h. The LH responses of cultured cells were measured after exposure to GnRH, A23187, or the phorbol ester phorbol 12,13 dibutyrate (PDB). The results indicated that the pituitary glands of the high Line contained significantly higher concentrations of GnRH receptors than did those of the low Line and released significantly more LH after stimulation with either GnRH or the Ca2+-calmodulin or protein kinase C intracellular second messenger systems. Therefore, the between-Line Difference in the regulation of pituitary LH secretion occurs at a step distal to the stimulatory sites of action of A23187 and PDB.
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Effects of indirect selection for pituitary responsiveness to gonadotropin-releasing hormone on the storage and release of luteinizing hormone and follicle-stimulating hormone in prepubertal male lambs.
Biology of reproduction, 1995Co-Authors: N. P. Evans, J R Mcneilly, R. WebbAbstract:Divergent selection based on the LH response to a 5-micrograms dose of GnRH in 10-wk-old Finn Dorset ram lambs has created two Lines of sheep that differ significantly in their response to both physiological and pharmacological dosages of GnRH. The aims of this study were to investigate whether there are between-Line Differences in endogenous LH and FSH secretion in ram lambs, as in the adult ewes, and to determine whether these Differences are related to Differences in storage of gonadotropins within the pituitary glands of the two Lines. To address the first aim, endogenous LH and FSH secretion was monitored in 20 ram lambs from each Line for a 6-h period at 2, 6, and 10 wk of age. To investigate potential between-Line Differences in gonadotropin storage, the LH responses to two acute challenges with either 0.5, 5.0, or 50.0 micrograms of GnRH were examined in 10-wk-old ram lambs from each Line. The results demonstrated that the between-Line Difference in the LH response to a 5-micrograms GnRH challenge in ram lambs is accompanied by significant between-Line Differences in the regulation of endogenous gonadotropin secretion. Specifically, lambs from the High Line secreted LH pulses of significantly greater amplitude than did lambs from the low Line at 2 and 10 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS)
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Alterations in endogenous gonadotropin secretion and pituitary responsiveness to gonadotropin-releasing hormone in adult ewes, following indirect selection in prepubertal male lambs.
Biology of reproduction, 1994Co-Authors: N. P. Evans, J R Mcneilly, R. WebbAbstract:Indirect selection to improve reproductive performance in the female, through use of a physiologically related trait in prepubertal males, the LH response to a GnRH challenge, has created two Lines of sheep with altered pituitary gland sensitivity to both physiological and pharmacological doses of GnRH. These Lines also exhibit correlated between-Line Differences in female reproductive performance during the first, and at the beginning of the second, breeding season. This study was designed to determine whether the observed between-Line Differences in female reproductive performance were related to between-Line Differences in endogenous gonadotropin secretion during the luteal and follicular phases of the estrous cycle and whether the between-Line Difference in the LH response to a GnRH challenge was maintained in adult females. The results indicated that, despite similar mean gonadotropin and steroid concentrations during the luteal and follicular phases of the estrous cycle, significant between-Line Differences in LH pulse amplitude were present during the follicular phase (high Line > low Line). In addition, the results indicated that the between-Line Difference in the LH response to a GnRH challenge was maintained in adult ewes, being most apparent during the follicular phase, when the magnitude of the Difference was similar to that in prepubertal female lambs. Therefore, in addition to showing maintenance of the between-Line Difference in the selected characteristic in postpubertal females, the results demonstrate that adult ewes from the two Lines differ in additional, unselected but physiologically related traits and provide a model system with which to study steroidal regulation of gonadotropin secretion in the ewe.
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Role of gonadal negative feedback on the gonadotrophin responses to gonadotrophin-releasing hormone (GnRH) in ram lambs from two Lines of sheep selected for their luteinizing hormone response to GnRH.
Journal of reproduction and fertility, 1991Co-Authors: N. P. Evans, J R Mcneilly, R. B. Land, R. WebbAbstract:Divergent selection has resulted in two Lines of lambs (high and low) that have a 5-fold Difference in their ability to release luteinizing hormone (LH) in response to 5 micrograms of gonadotrophin-releasing hormone (GnRH). BaseLine gonadotrophin concentrations, the gonadotrophin responses to a GnRH challenge and the concentrations of testosterone and oestradiol were compared in lambs which were castrated at birth and intact lambs from both selection Lines at 2, 6, 10 and 20 weeks of age. The pattern of LH and follicle-stimulating hormone (FSH) secretion was similar in the two Lines, but differed between the intact and the castrated lambs. Basal LH and FSH secretion were significantly higher in the castrates than in the intact lambs from both selection Lines. The high-Line lambs had significantly higher basal FSH concentrations at all ages tested and significantly higher basal LH concentrations during the early postnatal period. The magnitude of the gonadotrophin responses to GnRH differed significantly between the intact and the castrated lambs within each Line, the amount of gonadotrophins secreted by the castrated lambs being significantly greater. The removal of gonadal negative feedback by castration did not alter the between-Line Difference in either LH or the FSH response to the GnRH challenge. Throughout the experimental period, the concentration of testosterone in the intact lambs was significantly greater than in the castrated lambs in both selection Lines, but no significant Difference was seen in the concentrations of oestradiol. No significant between-Line Differences were found in the peripheral concentrations of testosterone or oestradiol in the intact lambs from the two selection Lines. Therefore, despite similar amounts of gonadal negative feedback in the selection Lines, there were significant between-Line Differences in basal gonadotrophin concentrations, at 2 and 6 weeks of age, and in the LH and FSH responses to an exogenous GnRH challenge, at all ages tested. Removal of gonadal negative feedback did not affect the magnitude of the between-Line Difference in the response of the Lines to GnRH stimulation. The results indicate that the effects of selection on gonadotrophin secretion are primarily at the level of the hypothalamo-pituitary complex.
N. P. Evans - One of the best experts on this subject based on the ideXlab platform.
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Extra- and intracellular effects of divergent selection for pituitary responsiveness to gonadotropin-releasing hormone in prepubertal ram lambs.
Biology of reproduction, 1997Co-Authors: N. P. Evans, J R Mcneilly, T. A. Bramley, R. WebbAbstract:Divergent selection based on the response of 10-wk-old male lambs to a GnRH challenge has produced two Lines of sheep, referred to as high and low Lines, that differ in their ability to release LH in response to pharmacological and physiological doses of GnRH. The aim of this study was to determine whether the between-Line Differences in pituitary sensitivity were related to Differences in GnRH receptor number and/or the transduction of the intracellular signal following GnRH receptor activation. Pituitary glands were collected from fourteen 20-wk-old ram lambs from each Line, weighed, and sampled for GnRH receptor analysis. The remaining tissue from 9 lambs from each Line was dispersed. Of the resultant cell suspension, a sample was stored for measurement of GnRH receptor content and the remainder was plated and cultured for 24 h. The LH responses of cultured cells were measured after exposure to GnRH, A23187, or the phorbol ester phorbol 12,13 dibutyrate (PDB). The results indicated that the pituitary glands of the high Line contained significantly higher concentrations of GnRH receptors than did those of the low Line and released significantly more LH after stimulation with either GnRH or the Ca2+-calmodulin or protein kinase C intracellular second messenger systems. Therefore, the between-Line Difference in the regulation of pituitary LH secretion occurs at a step distal to the stimulatory sites of action of A23187 and PDB.
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Effects of indirect selection for pituitary responsiveness to gonadotropin-releasing hormone on the storage and release of luteinizing hormone and follicle-stimulating hormone in prepubertal male lambs.
Biology of reproduction, 1995Co-Authors: N. P. Evans, J R Mcneilly, R. WebbAbstract:Divergent selection based on the LH response to a 5-micrograms dose of GnRH in 10-wk-old Finn Dorset ram lambs has created two Lines of sheep that differ significantly in their response to both physiological and pharmacological dosages of GnRH. The aims of this study were to investigate whether there are between-Line Differences in endogenous LH and FSH secretion in ram lambs, as in the adult ewes, and to determine whether these Differences are related to Differences in storage of gonadotropins within the pituitary glands of the two Lines. To address the first aim, endogenous LH and FSH secretion was monitored in 20 ram lambs from each Line for a 6-h period at 2, 6, and 10 wk of age. To investigate potential between-Line Differences in gonadotropin storage, the LH responses to two acute challenges with either 0.5, 5.0, or 50.0 micrograms of GnRH were examined in 10-wk-old ram lambs from each Line. The results demonstrated that the between-Line Difference in the LH response to a 5-micrograms GnRH challenge in ram lambs is accompanied by significant between-Line Differences in the regulation of endogenous gonadotropin secretion. Specifically, lambs from the High Line secreted LH pulses of significantly greater amplitude than did lambs from the low Line at 2 and 10 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS)
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Alterations in endogenous gonadotropin secretion and pituitary responsiveness to gonadotropin-releasing hormone in adult ewes, following indirect selection in prepubertal male lambs.
Biology of reproduction, 1994Co-Authors: N. P. Evans, J R Mcneilly, R. WebbAbstract:Indirect selection to improve reproductive performance in the female, through use of a physiologically related trait in prepubertal males, the LH response to a GnRH challenge, has created two Lines of sheep with altered pituitary gland sensitivity to both physiological and pharmacological doses of GnRH. These Lines also exhibit correlated between-Line Differences in female reproductive performance during the first, and at the beginning of the second, breeding season. This study was designed to determine whether the observed between-Line Differences in female reproductive performance were related to between-Line Differences in endogenous gonadotropin secretion during the luteal and follicular phases of the estrous cycle and whether the between-Line Difference in the LH response to a GnRH challenge was maintained in adult females. The results indicated that, despite similar mean gonadotropin and steroid concentrations during the luteal and follicular phases of the estrous cycle, significant between-Line Differences in LH pulse amplitude were present during the follicular phase (high Line > low Line). In addition, the results indicated that the between-Line Difference in the LH response to a GnRH challenge was maintained in adult ewes, being most apparent during the follicular phase, when the magnitude of the Difference was similar to that in prepubertal female lambs. Therefore, in addition to showing maintenance of the between-Line Difference in the selected characteristic in postpubertal females, the results demonstrate that adult ewes from the two Lines differ in additional, unselected but physiologically related traits and provide a model system with which to study steroidal regulation of gonadotropin secretion in the ewe.
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Role of gonadal negative feedback on the gonadotrophin responses to gonadotrophin-releasing hormone (GnRH) in ram lambs from two Lines of sheep selected for their luteinizing hormone response to GnRH.
Journal of reproduction and fertility, 1991Co-Authors: N. P. Evans, J R Mcneilly, R. B. Land, R. WebbAbstract:Divergent selection has resulted in two Lines of lambs (high and low) that have a 5-fold Difference in their ability to release luteinizing hormone (LH) in response to 5 micrograms of gonadotrophin-releasing hormone (GnRH). BaseLine gonadotrophin concentrations, the gonadotrophin responses to a GnRH challenge and the concentrations of testosterone and oestradiol were compared in lambs which were castrated at birth and intact lambs from both selection Lines at 2, 6, 10 and 20 weeks of age. The pattern of LH and follicle-stimulating hormone (FSH) secretion was similar in the two Lines, but differed between the intact and the castrated lambs. Basal LH and FSH secretion were significantly higher in the castrates than in the intact lambs from both selection Lines. The high-Line lambs had significantly higher basal FSH concentrations at all ages tested and significantly higher basal LH concentrations during the early postnatal period. The magnitude of the gonadotrophin responses to GnRH differed significantly between the intact and the castrated lambs within each Line, the amount of gonadotrophins secreted by the castrated lambs being significantly greater. The removal of gonadal negative feedback by castration did not alter the between-Line Difference in either LH or the FSH response to the GnRH challenge. Throughout the experimental period, the concentration of testosterone in the intact lambs was significantly greater than in the castrated lambs in both selection Lines, but no significant Difference was seen in the concentrations of oestradiol. No significant between-Line Differences were found in the peripheral concentrations of testosterone or oestradiol in the intact lambs from the two selection Lines. Therefore, despite similar amounts of gonadal negative feedback in the selection Lines, there were significant between-Line Differences in basal gonadotrophin concentrations, at 2 and 6 weeks of age, and in the LH and FSH responses to an exogenous GnRH challenge, at all ages tested. Removal of gonadal negative feedback did not affect the magnitude of the between-Line Difference in the response of the Lines to GnRH stimulation. The results indicate that the effects of selection on gonadotrophin secretion are primarily at the level of the hypothalamo-pituitary complex.
J K Belknap - One of the best experts on this subject based on the ideXlab platform.
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Mu-opiate receptor binding is up-regulated in mice selectively bred for high stress-induced analgesia.
Brain research, 1994Co-Authors: J S Mogil, P Marek, L A O'toole, M L Helms, B Sadowski, J C Liebeskind, J K BelknapAbstract:Pain perception and sensitivity to opiate analgesics strongly depend on genotype. Mice selectively bred for high (HA) and low (LA) swim stress-induced analgesia display markedly divergent morphine analgesia, a Difference that appears to be determined by one or at the most two major genes. In an attempt to provide candidate genes mediating the supranormal analgesia displayed by HA mice, we performed mu-opiate receptor binding on 27th generation HA, LA, and control (C) mice using [3H]naloxone. HA mice were found to have significantly higher whole-brain receptor density (Bmax) than LA mice in whole brain homogenates; no significant Difference in affinity (Kd) was observed. Quantitative autoradiography confirmed the Line Difference in whole-brain receptor binding. In the medial thalamus, a brain area implicated in ascending pathways of pain inhibition, HA mice were found to display significantly higher [3H]naloxone binding than C mice (a 64% increase) and LA mice (a 128% increase). No significant Line Differences were observed in any other brain locus. Thalamic mu receptors may therefore play an important role in a central 'volume control' mechanism of pain inhibition, and underlie individual Differences in the responses of mice to opiate analgesic drugs.
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μ-Opiate receptor binding is up-regulated in mice selectively bred for high stress-induced analgesia
Brain Research, 1994Co-Authors: J S Mogil, P Marek, L A O'toole, M L Helms, B Sadowski, J C Liebeskind, J K BelknapAbstract:Abstract Pain perception and sensitivity to opiate analgesics strongly depend on genotype. Mice selectively bred for high (HA) and low (LA) swim stress-induced analgesia display markedly divergent morphine analgesia, a Difference that appears to be determined by one or at the most two major genes. In an attempt to provide candidate genes mediating the supranormal analgesia displayed by HA mice, we performed μ-opiate receptor binding on 27th generation HA, LA, and control (C) mice using [ 3 H]naloxone. HA mice were found to have significantly higher whole-brain receptor density ( B max ) than LA mice in whole brain homogenates; no significant Difference in affinity ( K d ) was observed. Quantitative autoradiography confirmed the Line Difference in whole-brain receptor binding. In the medial thalamus, a brain area implicated in ascending pathways of pain inhibition, HA mice were found to display significantly higher [ 3 H]naloxone binding than C mice (a 64% increase) and LA mice (a 128% increase). No significant Line Differences were observed in any other brain locus. Thalamic μ receptors may therefore play an important role in a central ‘volume control’ mechanism of pain inhibition, and underlie individual Differences in the responses of mice to opiate analgesic drugs.
J R Mcneilly - One of the best experts on this subject based on the ideXlab platform.
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Extra- and intracellular effects of divergent selection for pituitary responsiveness to gonadotropin-releasing hormone in prepubertal ram lambs.
Biology of reproduction, 1997Co-Authors: N. P. Evans, J R Mcneilly, T. A. Bramley, R. WebbAbstract:Divergent selection based on the response of 10-wk-old male lambs to a GnRH challenge has produced two Lines of sheep, referred to as high and low Lines, that differ in their ability to release LH in response to pharmacological and physiological doses of GnRH. The aim of this study was to determine whether the between-Line Differences in pituitary sensitivity were related to Differences in GnRH receptor number and/or the transduction of the intracellular signal following GnRH receptor activation. Pituitary glands were collected from fourteen 20-wk-old ram lambs from each Line, weighed, and sampled for GnRH receptor analysis. The remaining tissue from 9 lambs from each Line was dispersed. Of the resultant cell suspension, a sample was stored for measurement of GnRH receptor content and the remainder was plated and cultured for 24 h. The LH responses of cultured cells were measured after exposure to GnRH, A23187, or the phorbol ester phorbol 12,13 dibutyrate (PDB). The results indicated that the pituitary glands of the high Line contained significantly higher concentrations of GnRH receptors than did those of the low Line and released significantly more LH after stimulation with either GnRH or the Ca2+-calmodulin or protein kinase C intracellular second messenger systems. Therefore, the between-Line Difference in the regulation of pituitary LH secretion occurs at a step distal to the stimulatory sites of action of A23187 and PDB.
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Effects of indirect selection for pituitary responsiveness to gonadotropin-releasing hormone on the storage and release of luteinizing hormone and follicle-stimulating hormone in prepubertal male lambs.
Biology of reproduction, 1995Co-Authors: N. P. Evans, J R Mcneilly, R. WebbAbstract:Divergent selection based on the LH response to a 5-micrograms dose of GnRH in 10-wk-old Finn Dorset ram lambs has created two Lines of sheep that differ significantly in their response to both physiological and pharmacological dosages of GnRH. The aims of this study were to investigate whether there are between-Line Differences in endogenous LH and FSH secretion in ram lambs, as in the adult ewes, and to determine whether these Differences are related to Differences in storage of gonadotropins within the pituitary glands of the two Lines. To address the first aim, endogenous LH and FSH secretion was monitored in 20 ram lambs from each Line for a 6-h period at 2, 6, and 10 wk of age. To investigate potential between-Line Differences in gonadotropin storage, the LH responses to two acute challenges with either 0.5, 5.0, or 50.0 micrograms of GnRH were examined in 10-wk-old ram lambs from each Line. The results demonstrated that the between-Line Difference in the LH response to a 5-micrograms GnRH challenge in ram lambs is accompanied by significant between-Line Differences in the regulation of endogenous gonadotropin secretion. Specifically, lambs from the High Line secreted LH pulses of significantly greater amplitude than did lambs from the low Line at 2 and 10 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS)
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Alterations in endogenous gonadotropin secretion and pituitary responsiveness to gonadotropin-releasing hormone in adult ewes, following indirect selection in prepubertal male lambs.
Biology of reproduction, 1994Co-Authors: N. P. Evans, J R Mcneilly, R. WebbAbstract:Indirect selection to improve reproductive performance in the female, through use of a physiologically related trait in prepubertal males, the LH response to a GnRH challenge, has created two Lines of sheep with altered pituitary gland sensitivity to both physiological and pharmacological doses of GnRH. These Lines also exhibit correlated between-Line Differences in female reproductive performance during the first, and at the beginning of the second, breeding season. This study was designed to determine whether the observed between-Line Differences in female reproductive performance were related to between-Line Differences in endogenous gonadotropin secretion during the luteal and follicular phases of the estrous cycle and whether the between-Line Difference in the LH response to a GnRH challenge was maintained in adult females. The results indicated that, despite similar mean gonadotropin and steroid concentrations during the luteal and follicular phases of the estrous cycle, significant between-Line Differences in LH pulse amplitude were present during the follicular phase (high Line > low Line). In addition, the results indicated that the between-Line Difference in the LH response to a GnRH challenge was maintained in adult ewes, being most apparent during the follicular phase, when the magnitude of the Difference was similar to that in prepubertal female lambs. Therefore, in addition to showing maintenance of the between-Line Difference in the selected characteristic in postpubertal females, the results demonstrate that adult ewes from the two Lines differ in additional, unselected but physiologically related traits and provide a model system with which to study steroidal regulation of gonadotropin secretion in the ewe.
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Role of gonadal negative feedback on the gonadotrophin responses to gonadotrophin-releasing hormone (GnRH) in ram lambs from two Lines of sheep selected for their luteinizing hormone response to GnRH.
Journal of reproduction and fertility, 1991Co-Authors: N. P. Evans, J R Mcneilly, R. B. Land, R. WebbAbstract:Divergent selection has resulted in two Lines of lambs (high and low) that have a 5-fold Difference in their ability to release luteinizing hormone (LH) in response to 5 micrograms of gonadotrophin-releasing hormone (GnRH). BaseLine gonadotrophin concentrations, the gonadotrophin responses to a GnRH challenge and the concentrations of testosterone and oestradiol were compared in lambs which were castrated at birth and intact lambs from both selection Lines at 2, 6, 10 and 20 weeks of age. The pattern of LH and follicle-stimulating hormone (FSH) secretion was similar in the two Lines, but differed between the intact and the castrated lambs. Basal LH and FSH secretion were significantly higher in the castrates than in the intact lambs from both selection Lines. The high-Line lambs had significantly higher basal FSH concentrations at all ages tested and significantly higher basal LH concentrations during the early postnatal period. The magnitude of the gonadotrophin responses to GnRH differed significantly between the intact and the castrated lambs within each Line, the amount of gonadotrophins secreted by the castrated lambs being significantly greater. The removal of gonadal negative feedback by castration did not alter the between-Line Difference in either LH or the FSH response to the GnRH challenge. Throughout the experimental period, the concentration of testosterone in the intact lambs was significantly greater than in the castrated lambs in both selection Lines, but no significant Difference was seen in the concentrations of oestradiol. No significant between-Line Differences were found in the peripheral concentrations of testosterone or oestradiol in the intact lambs from the two selection Lines. Therefore, despite similar amounts of gonadal negative feedback in the selection Lines, there were significant between-Line Differences in basal gonadotrophin concentrations, at 2 and 6 weeks of age, and in the LH and FSH responses to an exogenous GnRH challenge, at all ages tested. Removal of gonadal negative feedback did not affect the magnitude of the between-Line Difference in the response of the Lines to GnRH stimulation. The results indicate that the effects of selection on gonadotrophin secretion are primarily at the level of the hypothalamo-pituitary complex.
J S Mogil - One of the best experts on this subject based on the ideXlab platform.
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Mu-opiate receptor binding is up-regulated in mice selectively bred for high stress-induced analgesia.
Brain research, 1994Co-Authors: J S Mogil, P Marek, L A O'toole, M L Helms, B Sadowski, J C Liebeskind, J K BelknapAbstract:Pain perception and sensitivity to opiate analgesics strongly depend on genotype. Mice selectively bred for high (HA) and low (LA) swim stress-induced analgesia display markedly divergent morphine analgesia, a Difference that appears to be determined by one or at the most two major genes. In an attempt to provide candidate genes mediating the supranormal analgesia displayed by HA mice, we performed mu-opiate receptor binding on 27th generation HA, LA, and control (C) mice using [3H]naloxone. HA mice were found to have significantly higher whole-brain receptor density (Bmax) than LA mice in whole brain homogenates; no significant Difference in affinity (Kd) was observed. Quantitative autoradiography confirmed the Line Difference in whole-brain receptor binding. In the medial thalamus, a brain area implicated in ascending pathways of pain inhibition, HA mice were found to display significantly higher [3H]naloxone binding than C mice (a 64% increase) and LA mice (a 128% increase). No significant Line Differences were observed in any other brain locus. Thalamic mu receptors may therefore play an important role in a central 'volume control' mechanism of pain inhibition, and underlie individual Differences in the responses of mice to opiate analgesic drugs.
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μ-Opiate receptor binding is up-regulated in mice selectively bred for high stress-induced analgesia
Brain Research, 1994Co-Authors: J S Mogil, P Marek, L A O'toole, M L Helms, B Sadowski, J C Liebeskind, J K BelknapAbstract:Abstract Pain perception and sensitivity to opiate analgesics strongly depend on genotype. Mice selectively bred for high (HA) and low (LA) swim stress-induced analgesia display markedly divergent morphine analgesia, a Difference that appears to be determined by one or at the most two major genes. In an attempt to provide candidate genes mediating the supranormal analgesia displayed by HA mice, we performed μ-opiate receptor binding on 27th generation HA, LA, and control (C) mice using [ 3 H]naloxone. HA mice were found to have significantly higher whole-brain receptor density ( B max ) than LA mice in whole brain homogenates; no significant Difference in affinity ( K d ) was observed. Quantitative autoradiography confirmed the Line Difference in whole-brain receptor binding. In the medial thalamus, a brain area implicated in ascending pathways of pain inhibition, HA mice were found to display significantly higher [ 3 H]naloxone binding than C mice (a 64% increase) and LA mice (a 128% increase). No significant Line Differences were observed in any other brain locus. Thalamic μ receptors may therefore play an important role in a central ‘volume control’ mechanism of pain inhibition, and underlie individual Differences in the responses of mice to opiate analgesic drugs.