INVESTIGADORES
BALERIO Graciela Noemi
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 vol. 60 p. 132 - 140
ISSN:
0887-4476
Resumen:
ABSTRACT Although the expression of the morphine (MOR) withdrawal syndrome
is more marked in male mice than in females, we have demonstrated that the
GABAB agonist baclofen (BAC) is able to attenuate MOR withdrawal signs in either
sex. In order to extend these previous observations, the aim of the present study was
to evaluate the l-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 intraperitonial (i.p.) injection of MOR (2 mg/kg)
twice daily for 9 days. On the 10th day, dependent animals received naloxone (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 minutes after NAL, mice were sacrificed and
autoradiography with [3H]-[D-Ala2, N-Me-Phe4, -glycol5] enkephalin (DAMGO) was
carried out on mice brains at five different anatomical levels. Autoradiographic mapping
showed a significant increase of l-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was not significantly modified in any of the brain areas studied in withdrawn females.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 l-opioid receptor binding sites during MOR withdrawal only in
NAcC of males, and a similar tendency was observed in CPu and MDTh, even when it
was not statistically significant. 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 l-opioid receptor labeling in certain brain areas.