Influence of oxytocin on the central nervous system by different routes of administration
Maria V. Litvinova , llya Yu. Tissen , Andrei A. Lebedev , Evgenii R. Bychkov , Inessa V. Karpova , Petr D. Shabanov
Psychopharmacology & biological narcology ›› 2023, Vol. 14 ›› Issue (2) : 139 -148.
Influence of oxytocin on the central nervous system by different routes of administration
BACKGROUND: One of the unresolved problems in improving the pharmacotherapy of central nervous system diseases is the development and creation of technologies that allow drugs to cross the blood–brain barrier. One way to bypass the blood–brain barrier is the intranasal route of administration. Drug delivery is influenced by the peculiarities of the mechanism of transport of substances.
AIM: To examine the effect of intranasal administration of oxytocin on the behavior of mice and its content in various brain structures.
MATERIALS AND METHODS: The study used 60 outbred mice divided into six groups. Group 1 were healthy and did not receive oxytocin or physiological solution, groups 2 and 3 received single injection of 20 and 300 µL of oxytocin 5 IU intraperitoneally, respectively, group 4 was injected intranasally with 20 µL of oxytocin 5 IU, group 5 received 20 µL of saline intranasally, and group 6 received 300 µL of saline intraperitoneally. Behavioral effects were recorded in the elevated plus maze for 5 min, and the duration of stay in the open arm, number of transitions between the arms, and number of hangings from the arms were assessed. The concentration of oxytocin was measured in the following structures: olfactory bulb, striatum, hypothalamus, and hippocampus using an enzyme immunoassay.
RESULTS: Intranasal administration of oxytocin causes changes in behavior in mice, particularly a decrease in the degree of anxiety (anxiolytic effect). When timing the open arms in the plus maze test, mice administered intranasal oxytocin spent more time in the arms (32.44 ± 4.28 versus the control group with 5.66 ± 1.96 s), the number of transitions between the sleeves increased (1.90 ± 0.10 s versus 1.10 ± 0.10 s in the control group), and number of hangings from the sleeves increased (8.44 ± 1.37 versus 3.77 ± 0.98 in the control group). An increase was noted in one of the indicators — number of hangings from the sleeve after intraperitoneal injection of 300 µL of oxytocin, which may indicate the anxiolytic effect of oxytocin. The remaining groups receiving intranasal saline injection, intraperitoneal saline injection, and intraperitoneal injection of 20 µL of oxytocin did not show significant changes in behavior compared with the control group. In addition, after intranasal administration of oxytocin, its content increased in certain brain structures, i.e., the hypothalamus and hippocampus.
CONCLUSION: The results of this study indicate the potential efficacy of intranasal administration of oxytocin in the treatment of diseases affecting the central nervous system.
oxytocin / intranasal administration / blood–brain barrier / central nervous system drug delivery strategies / elevated plus maze
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