This study examined the effects of systemic administration of the
TrkB receptor antagonist (ANA-12) during induction of
morphine dependence on the severity of physical and psychological dependence and the cerebrospinal fluid (CSF)
BDNF levels in
morphine-dependent and withdrawn rats. Rats became
morphine-dependent by increasing daily doses of
morphine for 7 days, along with ANA-12 injection. 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) behaviors after spontaneous
morphine withdrawal. Also, the CSF
BDNF levels were assessed 2 h after the last dose of
morphine and day 13 after
morphine withdrawal in
morphine-dependent and withdrawn rats. We found that the
morphine withdrawal signs were significantly higher in
morphine dependent rats receiving ANA-12 on days of 5-7 after
morphine withdrawal, also ANA-12 exacerbated overall dependence severity. While, the percentage of time spent in the open arms and
sucrose preference were higher in
morphine-dependent rats receiving ANA-12 than
morphine-dependent rats receiving saline. Also, the ANA-12 injection decreased the CSF
BDNF levels following
morphine dependence, while increased it after
morphine withdrawal. We conclude that the ANA-12 exacerbated the severity of physical
morphine dependence but attenuated the anxiety/depressive-like behaviors in
morphine-dependent and withdrawn rats. Also, ANA-12 injection was able to reverse the changes in the CSF
BDNF levels. Therefore, ANA-12 is not more likely to complete treatment for
opiate addiction.