Alterations in the behavior, cognitive function, and BDNF level in adult male rats following neonatal blockade of GABA-A receptors

Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the mature brain. At an early developmental period, it acts in an excitatory manner that influences many processes of proliferation, migration, and differentiation of the neurons. Previous evidence indicated that manipulation of the GABAergic system function by activation or blockade of its receptors during developmental periods leads to behavioral and cognitive abnormality in adulthood. Therefore, we examined the effects of neonatal blockade of GABA-A receptors by bicuculline on behavior, cognitive function, and hippocampal and prefrontal cortex (PFC) brain-derived neurotrophic factors level (BDNF) in adulthood. As a result, neonatal rats were treated with either bicuculline (75,150, and 300 mu g/kg) or DMSO on postnatal days 7,9, and 11. These groups underwent the behavioral (open field, elevated plus maze, and hot plate) and learning and memory (passive avoidance learning and memory) tests in postnatal days (PNDs) 61-70. After the ending of the behavioral tests, the rats were sacrificed under deep anesthesia and the hippocampi and prefrontal cortex (PFC) of the brain were removed for assessing the BDNF mRNA expression. Our results indicated that neonatal administration of bicuculline at the highest dose increased passive avoidance memory and hippocampal BDNF level. Meanwhile, this drug at a low dose impaired this type of memory and increased PFC BDNF level. Besides, treatment with bicuculline during postnatal days increased anxiety and pain sensitivity in a dose-dependent manner. Taken together, these findings confirmed the notion that GABA-A receptors during the developmental period are important for programming neurobehavioral phenotypes in adult life.

Automated summary

The study found that blockade of GABA-A receptors in neonatal rats can affect neurobehavioral phenotypes in adulthood, with higher doses increasing passive avoidance memory and hippocampal BDNF levels, while lower doses impair this memory type and increase PFC BDNF levels. Additionally, drug treatment during the neonatal period increased anxiety and pain sensitivity in a dose-dependent manner. Overall, these results suggest the importance of GABA-A receptors in programming neurobehavioral phenotypes in adult life.