CREB Protein Expressed Differently in the Frontal Cortices of <i>Datura stramonium</i> Treated Rats: Implication for Addiction and Neurodegeneration

Abstract

Background: cAMP response element-binding protein (CREB) is one of the cellular transcription factors found in neurons. CREB is also important for the survival of neurons, and has an important role in the development of drug addiction. Datura stramonium ( DS ) is a tropical ubiquitous plant commonly used to increase the intoxication of certain beverages for recreational purposes. The seeds of this plant are very toxic and may produce addiction on prolong usage. This research investigated the effects of administration of high doses of DS seeds on the expression of CREB protein in both male and female rats’ frontal cortices and its implication in addiction and neurodegeneration. Materials and Methods: The study was conducted with a total of 24 male and female Wistar rats weighing 200 g - 250 g. The rats were divided into three groups of 8 rats each. Each group was further divided into four sub-groups of 2 rats each. Ethanolic dried seed extract of DS was diluted in normal saline and administered intraperitoneally (i.p.) to the treatment groups. The treated sub-groups received 750 mg/kg of DS extract once in group 1, twice in group 2 and thrice in group 3 daily for 4 weeks respectively, while the control sub-groups received i.p. normal saline concurrently for the same duration of time. The rats were euthanized and an analysis of variance (ANOVA) was computed to detect a significant main difference of DS effect on CREB expression for each group, while post hoc Bonferroni Test compared CREB protein expression between male and female groups. Result: There were significant differences in the expression of CREB protein between the sub-groups and between the male and female rats of treated sub-group (p < 0.05) compared to the controls. There was a decrease in the female treated sub-groups and an increase in the male treated sub-groups compared to the respective controls. Conclusion: High doses of DS administration for a prolong time may affect the expressions of CREB protein differently in male and female treated rats which may consequently lead to addiction and neurodegeneration affecting frontal cortex neurons.