Sexually dimorphic C-Fos expression during morphine withdrawal syndrome

INDUNI A; TARAVINI IR; BERNACCHIA F; ROSSELLI S; BALERIO G

Tandil, Buenos Aires, Argentina

Congreso; XL Reunión Anual de la Asociación Argentina de Farmacología Experimental; 2008

Asociación Argentina de Farmacología Experimental (SAFE)

&amp;amp;amp;amp;lt;!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:595.3pt 841.9pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --&amp;amp;amp;amp;gt; We have previousiy demonstrated sex differences during morphine (MOR) withdrawal. We have also shown that the GABAB agonist baclofen (BAC) was able to prevent the MOR withdrawal in male as well as female mice. The aim of the present study was to evaluate the immediate early gene c-Fos expression in various brain areas in mice of cither sex during naloxone (NAL)-precipitated withdrawal and its prevention with BAC. Swiss-Webster prepubertal mice were rendered dependent by i.p. injection of MOR (2 mg/kg), twice daily for 9 days. On the 10th day, dependent mice were divided into two groups: withdrawal group received NAL (6 mg/kg, i.p.) after the last dose of MOR, while prevention group received BAC (2 mg/kg, i.p.) before NAL injection.  Animals were anaesthetized and transcardially perfused with parafornaldehyde. Brains were removed and cut to perform immunohistochemical studies. Our results showed a significant decrease in c-Fos expression in CA3 (p<0.01), CA1 (p<0.01) and dentate gyrus (p<0.001) of the Hippocampus of MOR withdrawn males vs control groups. Conversely, the number of Fos positively nuclei was not modified in any of the areas studied of females. The pretreatment with BAC did not modify the c-Fos expression in MOR withdrawn males. The sexual dimorphism observed herein confirms the greater sensitivity of males in response to MOR. The effect of BAC in preventing the expression of MOR withdrawal would not be related with c-Fos expression.