BDNF Pretreatment Attenuates Morphine-Induced Learning and Memory Impairment in Rats

Background: It has been known that Brain-Derived Neurotrophic Factor (BDNF) is involved in neural survival and long term memory (LTM). Here we hypothesized that BDNF as a potent neurotrophic factor might modulate amnestic effect induced by morphine. Objectives: The aim of this study was to examine whether infusion of exogenous BDNF in the CA1 regions of the dorsal hippocampi could ameliorate memory impairment induced by morphine. Materials and Methods: Forty rats were divided into 5 groups for dose response study of morphine (2.5, 5, 7.5 and 10 mg/kg morphine, and saline, intraperitoneal) on memory retention. For second part of the experiment 24 animals were divided into three groups: (morphine +BDNF, morphine + saline and saline + saline). Two weeks after stereotaxic surgery, animals received 0.5 &mu;l bilateral infusion of either saline or BDNF (5 &micro;g/rat) intrahippocampally, 30 minutes before morphine treatment (7.5 mg/kg, i.p.). Step-through inhibitory avoidance task has been used to examine retrieval of memory formation, 1.5 and 24 h after the training. Results: The results showed that systemic administration of 7.5 and 10 mg/kg morphine compared with saline immediately after the training impairs long-term retention of memory for passive avoidance task in rats tested 24 hours later (p < 0.01). Surprisingly intra-CA1 microinjection of BDNF 30 minutes prior to injection of morphine significantly prevented amnesia (p < 0.001). Conclusions: These findings suggested that increase the level of BDNF in the CA1 region of the hippocampus during 30 minutes time window before morphine administration might modulate morphine-induced amnesia.