Intranasal administration of testosterone increased immobile-sniffing, exploratory behavior, motor behavior and grooming behavior in rats

Currently, testosterone (T) replacement therapy is typically provided by oral medication, injectable T esters, surgically implanted T pellets, transdermal patches and gels. However, most of these methods of administration are still not ideal for targeting the central nervous system. Recently, therapeutic intranasal T administration (InT) has been considered as another option for delivering T to the brain. In the present study, the effects of 21-day InT treatment were assessed on open field behavior in gonadectomized (GDX) rats and intact rats. Subcutaneous injections of T at same dose were also tested in GDX rats. A total of 12 behavioral events were examined in GDX groups with or without T and in intact groups with or without InT. Significant decreases in open field activity were observed in rats after GDX without InT compared to sham-operated rats. The open field activity scores for most tests significantly increased with InT treatment in GDX rats and in intact rats compared with the corresponding GDX rats and intact rats. Intranasal administration of T improved the reduced behaviors resulted from T deficiency better than subcutaneous injection of T, demonstrating that T can be delivered to the brain by intranasal administration. Our results suggest that intranasal T delivery is an effective option for targeting the central nervous system.

Research highlights
► The model of testosterone deficiency was prepared by gonadectomy of the male rats.
► A total of 12 behavioral events were examined in the open field behavioral test.
► Gonadectomy decreased the open field behavior activities in rats.
► Chronic intranasal administration of testosterone increased the behavior activities.
► Intranasal route improved the impaired behaviors better than subcutaneous injection.