Role of the sex in morphine properties: Relationship to plasma morphine and naloxone levels

DIAZ S, HERMIDA P, JOANNAS L, GARCÍA C, VILLAAMIL E, RIDOLFI A, OLIVERA M, RUBIO M, BALERIO G.

Mar del Plata

Congreso; XXXVII Reunión Anual de Comunicaciones Científicas.; 2005

Sociedad Argentina de Farmacología Experimental

Role of the sex in morphine properties: Relationship to plasma morphine and naloxone levels. 1,2Diaz S, 1,2Hermida P, 1Joannas L, 1García C, 3Villaamil E, 3Ridolfi A, 3Olivera M, 1,2Rubio M, 1,2Balerio G. 1ININFA (CONICET), 2Cát. de Farmacología, 3Cát. de Toxicología, FFyB (UBA) Junín 956 5º piso, Bs. As. sildiaz@ffyb.uba.ar Sex differences have been observed for morphine (MOR) analgesia as well as for MOR withdrawal syndrome precipitated by naloxone (NAL). Our purpose was to evaluate the involvement of the sex in the analgesic response to chronic MOR and NAL-precipitated withdrawal and whether these possible sex differences might be due to differences in MOR and NAL plasma levels. Swiss mice were rendered dependent by i.p. injection of MOR (2 mg/kg), twice daily for 9 days. On the 10th day dependent mice received NAL (6 mg/kg, i.p.) after MOR. The analgesic response and withdrawal signs were determined by the hot plate and the open field, respectively. In addition, MOR and NAL plasma levels were measured by GC and HPLC, respectively at different times. No sex differences were found for the analgesic response to chronic MOR, whereas the expression of MOR withdrawal signs was more marked in males Pharmacokinetic analysis showed a slight difference between male and female MOR concentration curves, whereas no sex differences were observed between NAL disposition curves. The analysis of kinetic and dynamic results also indicates a delay between the time-course of MOR plasma levels and the time-course of the analgesic effect in either sex. In conclusion, although males and females respond differentially to NAL-precipitated withdrawal, a pharmacokinetic factor would not appear to influence this dimorphic behavior, while no involvement of sex was found in the analgesic response to chronic MOR.