Analysis of brain mu-opioid receptor binding during morphine dependence and withdrawal in mice

DIAZ S., KEMMLING A., BONAVITA C., RUBIO M., BALERIO G.

Corrientes

Congreso; XXXIII Reunión Anual de Comunicaciones Científicas.; 2001

Asociación Argentina de Farmacología Experimental

Analysis of brain m-opioid receptor binding during morphine dependence and withdrawal in mice. Diaz S, Kemmling A, Bonavita C, Balerio G. Cát. de Farmacología, FFYB (UBA) e ININFA (CONICET), Junín 956 5º piso (1113), Buenos Aires. Email: gbalerio@ffyb.uba.ar In previous studies we demonstrated behavioral and neurochemical sex differences in the expression of the morphine (MOR) withdrawal syndrome in mice. The aim of this study was to compare the m-opioid receptor binding in whole brain of MOR dependent and abstinent male and female mice. Swiss-Webster albino mice (27-33g) were rendered dependent by i.p. injection of MOR (2 mg/kg), twice daily for 9 days. On the tenth day, dependent mice were divided into two groups: abstinence group received the opioid antagonist naloxone (6 mg/kg, i.p.) after the last dose of MOR in order to precipitate the withdrawal syndrome, while dependence group received saline. After these treatments, mice were killed and the density and affinity of m-opioid receptors to ([3H]-DAMGO) were investigated (Chan KW et al., Eur J Pharmacol 1997, 319: 225-8). Results (mean ± SEM) were as follows:                      MALE                              FEMALE                             Kd             Bmax                 Kd             Bmax Dependence   1.3 ± 0.2    171.2 ± 12.6      1.3 ± 0.1     181.8 ± 16.4          Abstinence     1.3 ± 0.2    195.9 ± 12.2      1.5 ± 0.3     206.2 ± 8.7 Saline control 1.1 ± 0.1    186.8 ± 11.2      1.3 ± 0.2     174.9 ± 10.6 These data indicate that no significant alteration in affinity and density occur in dependent as well as in abstinent mice. Sex differences were not observed for m-binding sites. These results suggest that pharmacologic sex differences in the expression of the MOR withdrawal syndrome in mice, would not be related with changes in central nervous system m-opioid receptor binding .