Gender- and age-dependent effects on the severity of morphine dependence are still controversial. The aim of this study was to investigate the effects of age and sex on the severity of physical and psychological dependence in morphine-dependent rats. The adult/aged male and female Wistar rats were chronically treated with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine for 14 days. Then, rats were tested for the severity of physical dependence on morphine (spontaneous withdrawal signs), anxiety-like (the elevated plus maze), depressive-like (sucrose preference test) and grooming behaviors after spontaneous morphine withdrawal. We found that the morphine withdrawal signs decreased after 3 and 7 days of withdrawal in female and male rats respectively, while there was no significant difference in overall dependence severity between the two sexes or ages. Also, we found that the withdrawal of morphine led to increased anxiety, depression and obsessive-compulsive behavior in the D (dependent)/Adult male and female rats. Also, the D/aged female and male rats exhibited a reduction in depressive-like behavior than the D/Adult rats. Moreover, the D/female rats exhibited a decreased obsessive-compulsive behavior in both age groups than male rats. We conclude that age has no effect on the duration of withdrawal from morphine and overall dependence severity. While, the duration of withdrawal from morphine was lower in female than male rats. Our results showed a sex difference on the duration of morphine withdrawal and an age difference in the expression of psychological dependence on morphine. Thus, therapeutic strategies may be different for opiate-dependent individuals in physical and psychological dimensions.
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