ININFA 02677
INSTITUTO DE INVESTIGACIONES FARMACOLOGICAS
Unidad Ejecutora - UE
artículos
Título:
Morphine withdrawal syndrome and its prevention with baclofen: autoradiographic study of µ-opioid receptors in prepubertal male and female mice
Autor/es:
SILVINA L. DIAZ, VIRGINIA G. BARROS, MARTA C. ANTONELLI, MODESTO C. RUBIO AND GRACIELA N. BALERIO
Revista:
SYNAPSE
Referencias:
Año: 2006
ISSN:
0887-4476
Resumen:
We have previously shown that the GABAB agonist baclofen (BAC) prevents the expression
of morphine (MOR) withdrawal syndrome in male as well as female mice. In order to extend
these previous observations, the aim of the present study was to evaluate the µ-opioid receptor
labeling in various brain areas in mice of either sex, during MOR withdrawal and its
prevention with BAC. Prepubertal Swiss-Webster mice were rendered dependent by
intraperitoneal (i.p.) injection of MOR (2 mg/kg), twice daily for 9 days. On the 10th day,
dependent animals received NAL (6 mg/kg, i.p.) 60 min after MOR, and another pool of
dependent mice received BAC (2 mg/kg, i.p.) previous to NAL. Thirty min after NAL
injection mice were sacrificed, brains were collected, and coronal sections were cut to
perform autoradiographic studies with [3H]-[DAMGO]. Autoradiographic mapping showed a
significant increase of µ-opioid receptor labeling during MOR withdrawal in nucleus
accumbens core (NAcC), caudate putamen (CPu), mediodorsal thalamic nucleus (MDTh),
basolateral and basomedial amygdala and ventral tegmental area vs respective control groups
in male mice. In contrast, opiate receptor labeling was not significantly modified in any of the
brain areas studied in withdrawn females. BAC reestablished µ-opioid receptor binding sites
during MOR withdrawal only in NAcC, CPu and MDTh of males. The sexual dimorphism
observed in the present study confirms previous reports indicating a greater sensitivity of
males in response to MOR pharmacological properties. The present results suggest that the
effect of BAC in preventing the expression of MOR withdrawal signs could be related with
the ability of BAC to reestablish the µ-opioid receptor labeling in certain brain areas.B agonist baclofen (BAC) prevents the expression
of morphine (MOR) withdrawal syndrome in male as well as female mice. In order to extend
these previous observations, the aim of the present study was to evaluate the µ-opioid receptor
labeling in various brain areas in mice of either sex, during MOR withdrawal and its
prevention with BAC. Prepubertal Swiss-Webster mice were rendered dependent by
intraperitoneal (i.p.) injection of MOR (2 mg/kg), twice daily for 9 days. On the 10th day,
dependent animals received NAL (6 mg/kg, i.p.) 60 min after MOR, and another pool of
dependent mice received BAC (2 mg/kg, i.p.) previous to NAL. Thirty min after NAL
injection mice were sacrificed, brains were collected, and coronal sections were cut to
perform autoradiographic studies with [3H]-[DAMGO]. Autoradiographic mapping showed a
significant increase of µ-opioid receptor labeling during MOR withdrawal in nucleus
accumbens core (NAcC), caudate putamen (CPu), mediodorsal thalamic nucleus (MDTh),
basolateral and basomedial amygdala and ventral tegmental area vs respective control groups
in male mice. In contrast, opiate receptor labeling was not significantly modified in any of the
brain areas studied in withdrawn females. BAC reestablished µ-opioid receptor binding sites
during MOR withdrawal only in NAcC, CPu and MDTh of males. The sexual dimorphism
observed in the present study confirms previous reports indicating a greater sensitivity of
males in response to MOR pharmacological properties. The present results suggest that the
effect of BAC in preventing the expression of MOR withdrawal signs could be related with
the ability of BAC to reestablish the µ-opioid receptor labeling in certain brain areas.th day,
dependent animals received NAL (6 mg/kg, i.p.) 60 min after MOR, and another pool of
dependent mice received BAC (2 mg/kg, i.p.) previous to NAL. Thirty min after NAL
injection mice were sacrificed, brains were collected, and coronal sections were cut to
perform autoradiographic studies with [3H]-[DAMGO]. Autoradiographic mapping showed a
significant increase of µ-opioid receptor labeling during MOR withdrawal in nucleus
accumbens core (NAcC), caudate putamen (CPu), mediodorsal thalamic nucleus (MDTh),
basolateral and basomedial amygdala and ventral tegmental area vs respective control groups
in male mice. In contrast, opiate receptor labeling was not significantly modified in any of the
brain areas studied in withdrawn females. BAC reestablished µ-opioid receptor binding sites
during MOR withdrawal only in NAcC, CPu and MDTh of males. The sexual dimorphism
observed in the present study confirms previous reports indicating a greater sensitivity of
males in response to MOR pharmacological properties. The present results suggest that the
effect of BAC in preventing the expression of MOR withdrawal signs could be related with
the ability of BAC to reestablish the µ-opioid receptor labeling in certain brain areas.3H]-[DAMGO]. Autoradiographic mapping showed a
significant increase of µ-opioid receptor labeling during MOR withdrawal in nucleus
accumbens core (NAcC), caudate putamen (CPu), mediodorsal thalamic nucleus (MDTh),
basolateral and basomedial amygdala and ventral tegmental area vs respective control groups
in male mice. In contrast, opiate receptor labeling was not significantly modified in any of the
brain areas studied in withdrawn females. BAC reestablished µ-opioid receptor binding sites
during MOR withdrawal only in NAcC, CPu and MDTh of males. The sexual dimorphism
observed in the present study confirms previous reports indicating a greater sensitivity of
males in response to MOR pharmacological properties. The present results suggest that the
effect of BAC in preventing the expression of MOR withdrawal signs could be related with
the ability of BAC to reestablish the µ-opioid receptor labeling in certain brain areas.vs respective control groups
in male mice. In contrast, opiate receptor labeling was not significantly modified in any of the
brain areas studied in withdrawn females. BAC reestablished µ-opioid receptor binding sites
during MOR withdrawal only in NAcC, CPu and MDTh of males. The sexual dimorphism
observed in the present study confirms previous reports indicating a greater sensitivity of
males in response to MOR pharmacological properties. The present results suggest that the
effect of BAC in preventing the expression of MOR withdrawal signs could be related with
the ability of BAC to reestablish the µ-opioid receptor labeling in certain brain areas.
